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Research Publications

Browse scientific publications from the NIH-funded RDCRN network and its 20 consortia or research teams to find information about rare disease research and read rare disease publications. Publications are sorted by consortium and year.

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Quantification of enlarged deep medullary vein volumes in Sturge-Weber syndrome. Jeong JW, Lee MH, Luat AF, Xuan Y, Haacke EM, Juhász C. Quant Imaging Med Surg. 2024 Feb 1;14(2):1916-1929. doi: 10.21037/qims-23-1271. Epub 2024 Jan 23. PMID: 38415136; PMCID: PMC10895099.

Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel formation in the brain, eyes, and skin at birth. In patients with SWS, enlarged deep medullary veins—mostly located in the white matter in the brain—may form early and can expand during the first years of life to provide compensatory collateral venous drainage of brain regions affected by leptomeningeal venous malformations localized on the brain surface.

The extent of enlarged deep veins during the early SWS disease course could be an imaging marker of this deep venous remodeling in an attempt to compensate for impaired brain surface venous blood flow. In this prospective imaging study, researchers used brain magnetic resonance imaging (MRI) to develop and optimize a quantitative approach to measure deep vein volumes in the affected brain of young patients with SWS and compare the findings to those of their healthy siblings. 

By combining two types of MRI (susceptibility-weighted imaging and volumetric T1 images), the authors were able to measure the volumes of deep veins, which were 10-12 fold higher than venous volumes in their healthy siblings. Greater deep vein volumes were associated with lower cortical surface area of the affected hemisphere, a measure of cortical atrophy. This new analytic approach of brain MRI can provide an objective way to assess the extent of deep venous remodeling in SWS and other disorders affecting the medullary veins of the brain.

A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([(18)F]GE-180) PET/MRI. Kim SJW, Lupo JM, Chen Y, Pampaloni MH, VanBrocklin HF, Narvid J, Kim H, Seo Y. Front Med (Lausanne). 2023 Apr 5;10:1091463. doi: 10.3389/fmed.2023.1091463. eCollection 2023.

Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. Kilian A, Latino GA, White AJ, Ratjen F, McDonald J, Whitehead KJ, Gossage JR, Krings T, Lawton MT, Kim H, Faughnan ME, The Brain Vascular Malformation Consortium Hht Investigator Group. J Clin Med. 2023 Apr 4;12(7):2704. doi: 10.3390/jcm12072704.

Deep Venous Remodeling in Unilateral Sturge-Weber Syndrome: Robust Hemispheric Differences and Clinical Correlates. Juhász C, Luat AF, Behen ME, Gjolaj N, Jeong JW, Chugani HT, Kumar A. Pediatr Neurol. 2023 Feb;139:49-58. doi: 10.1016/j.pediatrneurol.2022.11.011. Epub 2022 Nov 25. PMID: 36521316; PMCID: PMC9840672.

Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel development in the brain, eyes, and skin at birth. In patients with SWS, enlarged deep medullary veins (EDMVs)—located in the white matter in the brain—could allow for drainage of brain regions affected by leptomeningeal venous malformations (LVM), a type of vascular malformation of the brain. In this study, researchers evaluated the prevalence, extent, hemispheric differences, and clinical correlates of EDMVs in SWS. Fifty children with SWS underwent brain magnetic resonance imaging that included susceptibility weighted imaging, as well as neurocognitive evaluations. The team then assessed the extent of EDMVs, comparing between patients with right and left hemispheric SWS. Results show that EDMVs are common in SWS. For patients with right hemispheric SWS, extensive EDMVs appear to develop more commonly and earlier than in left hemispheric SWS. Authors note that deep venous remodeling may contribute to better clinical outcomes in some patients with SWS.

Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation. Weinsheimer S, Nelson J, Abla AA, Ko NU, Tsang C, Okoye O, Zabramski JM, Akers A, Zafar A, Mabray MC, Hart BL, Morrison L, McCulloch CE, Kim H; Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group. J Am Heart Assoc. 2023 Feb 7;12(3):e027572. doi: 10.1161/JAHA.122.027572. Epub 2023 Jan 25. PMID: 36695309; PMCID: PMC9973654.

Familial cerebral cavernous malformation (CCM) is an inherited disease characterized by abnormally enlarged spaces in the brain where blood collects near irregularly shaped, enlarged capillaries (tiny blood vessels) which have abnormally thin walls prone to leaking. CCM can cause intracranial hemorrhage (ICH), which can lead to death or long-term neurological damage. However, few studies have focused on ICH rates and risk factors in familial CCM.

In this study, researchers report ICH rates and assess whether CCM lesion burden—a disease severity marker—is associated with risk of symptomatic ICH in familial CCM. The team studied 386 patients with familial CCM with follow‐up data enrolled in the Brain Vascular Malformation Consortium CCM Project.

Results show that patients with familial CCM with a prior history of an ICH event are at higher risk for rehemorrhage during follow‐up. In addition, CCM lesion burden is significantly associated with an increased risk of subsequent symptomatic ICH. Authors note that these findings demonstrate the importance of lesion burden as a predictor of patient outcomes, which can also help to assess patient risk.

The Potential Role of MiRs-139-5p and -454-3p in Endoglin-Knockdown-Induced Angiogenic Dysfunction in HUVECs. Cannavicci A, Zhang Q, Kutryk MJB. Int J Mol Sci. 2023 Mar 3;24(5):4916. doi: 10.3390/ijms24054916.

A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis. Galeffi F, Snellings DA, Wetzel-Strong SE, Kastelic N, Bullock J, Gallione CJ, North PE, Marchuk DA. Angiogenesis. 2022 May 30. doi: 10.1007/s10456-022-09841-w. Epub ahead of print. PMID: 35635655.

Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel development in the brain, eyes, and skin at birth. A hallmark feature is capillary malformation, also known as a port-wine birthmark (a red, pink, or purple facial birthmark). SWS and capillary malformations are both caused by mutations in the GNAQ gene. In this study, researchers sequenced skin biopsies of capillary malformations from nine patients. They identified the same type of GNAQ mutation (R183Q) in nearly all samples. However, one sample exhibited a new type of GNAQ mutation (Q209R). To explore its effects, the team compared this new mutation with other GNAQ mutations. The authors found that although the different mutations varied in signaling strength, they all had the same effects in cells. Since some of these same mutations are also found in cancer, pharmaceutical companies are working on inhibiting the effects of this gene. Thus, drugs that may work for certain cancers with GNAQ mutations may also work for SWS.

A single-cell atlas of the normal and malformed human brain vasculature. Winkler EA, Kim CN, Ross JM, Garcia JH, Gil E, Oh I, Chen LQ, Wu D, Catapano JS, Raygor K, Narsinh K, Kim H, Weinsheimer S, Cooke DL, Walcott BP, Lawton MT, Gupta N, Zlokovic BV, Chang EF, Abla AA, Lim DA, Nowakowski TJ. Science. 2022 Mar 4;375(6584):eabi7377. doi: 10.1126/science.abi7377. Epub 2022 Mar 4.

Endoluminal Biopsy for Molecular Profiling of Human Brain Vascular Malformations. Winkler E, Wu D, Gil E, McCoy D, Narsinh K, Sun Z, Mueller K, Ross J, Kim H, Weinsheimer S, Berger M, Nowakowski T, Lim D, Abla A, Cooke D. Neurology. 2022 Apr 19;98(16):e1637-e1647. doi: 10.1212/WNL.0000000000200109. Epub 2022 Feb 10.

Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence. Sheth KN, Anderson CD, Biffi A, Dlamini N, Falcone GJ, Fox CK, Fullerton HJ, Greenberg SM, Hemphill JC, Kim A, Kim H, Ko NU, Roland JL, Sansing LH, van Veluw SJ, Rosand J. Stroke. 2022 Mar;53(3):1020-1029. doi: 10.1161/STROKEAHA.121.036197. Epub 2022 Feb 3.

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways. Cannavicci A, Zhang Q, Faughnan ME, Kutryk MJB. Genes (Basel). 2022 Apr 9;13(4):665. doi: 10.3390/genes13040665.

Neurovascular Complications and Pulmonary Arteriovenous Malformation Feeding Artery Size. Ananiadis T, Faughnan ME, Clark D, Prabhudesai V, Kim H, Lawton MT, Vozoris NT; Brain Vascular Malformation Consortium HHT Investigator Group. Ann Am Thorac Soc. 2022 Apr 20. doi: 10.1513/AnnalsATS.202202-130RL. Online ahead of print.

Quantification metrics for telangiectasia using optical coherence tomography. Cardinell JL, Ramjist JM, Chen C, Shi W, Nguyen NQ, Yeretsian T, Choi M, Chen D, Clark DS, Curtis A, Kim H, Faughnan ME, Yang VXD; Brain Vascular Malformation Consortium HHT Investigator Group. Sci Rep. 2022 Feb 2;12(1):1805. doi: 10.1038/s41598-022-05272-1.

Robotics for neuroendovascular intervention: Background and primer. Narsinh KH, Paez R, Mueller K, Caton MT, Baker A, Higashida RT, Halbach VV, Dowd CF, Amans MR, Hetts SW, Norbash AM, Cooke DL. Neuroradiol J. 2022 Feb;35(1):25-35. doi: 10.1177/19714009211034829. Epub 2021 Aug 16.

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation. Choksi F, Weinsheimer S, Nelson J, Pawlikowska L, Fox CK, Zafar A, Mabray MC, Zabramski J, Akers A, Hart BL, Morrison L, McCulloch CE, Kim H. Mol Genet Genomic Med. 2021 Sep 7:e1794. doi: 10.1002/mgg3.1794. Online ahead of print.

Cerebral cavernous malformations (CCMs) are collections of small blood vessels in the brain that are enlarged and irregular in structure, leading to altered blood flow. While approximately 25 percent of individuals with CCMs never experience any related medical problems, other people with CCMs may experience serious symptoms such as headaches, seizures, paralysis, hearing or vision deficiencies, and cerebral hemorrhage. In addition to lesions in the brain, familial cases have lesions present on the skin. Interestingly, similar appearing skin lesions have been reported in another inherited vascular disease called capillary malformation-arteriovenous malformation (CM-AVM), which is caused by mutations in RASA1 and EPHB4. In this study, researchers investigated whether common variants in the EPHB4 and RASA1 genes are associated with familial CCM disease severity, including intracranial hemorrhage (ICH), total lesions, and large lesion counts. They found that EPHB4 variants were not associated with CCM severity, but a common RASA1 variant may be associated with ICH and large lesion count. These findings could improve understanding of the natural history of CCM, leading to better predictions of disease course and new medical therapies for treatment.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention. Narsinh KH, Kilbride BF, Mueller K, Murph D, Copelan A, Massachi J, Vitt J, Sun CH, Bhat H, Amans MR, Dowd CF, Halbach VV, Higashida RT, Moore T, Wilson MW, Cooke DL, Hetts SW. Radiology. 2021 Apr;299(1):167-176. doi: 10.1148/radiol.2021202750. Epub 2021 Feb 9.

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations. Sabeti S, Ball KL, Bhattacharya SK, Bitrian E, Blieden LS, Brandt JD, Burkhart C, Chugani HT, Falchek SJ, Jain BG, Juhasz C, Loeb JA, Luat A, Pinto A, Segal E, Salvin J, Kelly KM. Pediatr Neurol. 2021 Aug;121:59-66. doi: 10.1016/j.pediatrneurol.2021.04.013. Epub 2021 May 6.

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation. Keränen S, Suutarinen S, Mallick R, Laakkonen JP, Guo D, Pawlikowska L, Jahromi BR, Rauramaa T, Ylä-Herttuala S, Marchuk D, Krings T, Koivisto T, Lawton M, Radovanovic I, Kim H, Faughnan ME, Frösen J. Acta Neurochir (Wien). 2021 Sep;163(9):2503-2514. doi: 10.1007/s00701-021-04895-z. Epub 2021 Jun 29.

Brain ateriovenous malformations (bAVM) are rare vascular anomalies that may bleed causing epilepsy, neurological deficits, or death. Cyclo-oxygenase-2 (COX2) is an enzyme that plays a key role in promoting inflammation. Researchers examined tissue samples from surgery of 139 patients with bAVMs and compared them to 21 normal samples. They were seeking to determine if COX2 is expressed in bAVMs and whether it associates with inflammation and hemorrhage in these lesions. They concluded that COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodeling and ongoing inflammation. Authors suggest that COX2 may be a target for drug therapy stabilizing bAVMs.  

Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells. Zhang Q, Wang C, Cannavicci A, Faughnan ME, Kutryk MJB. Transl Res. 2021 Sep;235:129-143. doi: 10.1016/j.trsl.2021.04.005. Epub 2021 Apr 22.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of the blood vessels that can cause excessive bleeding. People with HHT can develop abnormal blood vessels called arteriovenous malformations (AVMs) in several areas of the body, including the skin, brain, lungs, liver, or intestines. Endoglin (ENG) is one of the genes commonly mutated in this autosomal dominant disease. In this study, researchers sought to investigate the interplay of the ENG gene with several other genes in endothelial cells. They found that ENG deficiency alters the vascular endothelial growth factor (VEGF)/VEGFR2 pathway, which may play a role in the development of HHT.

Identification of a Mosaic Activating Mutation in GNA11 in Atypical Sturge-Weber Syndrome. Thorpe J, Frelin LP, McCann M, Pardo CA, Cohen BA, Comi AM, Pevsner J. J Invest Dermatol. 2021 Mar;141(3):685-688. doi: 10.1016/j.jid.2020.03.978. Epub 2020 Aug 7.

Intracranial hemorrhage due to central venous occlusion from hemodialysis access: A case report. Mirza MH, Schwertner A, Kohlbrenner R, Dowd CF, Narsinh KH. Interdiscip Neurosurg. 2021 Jun;24:101081. doi: 10.1016/j.inat.2020.101081. Epub 2021 Jan 4.

Intrasaccular flow disruption (WEB) of a large wide-necked basilar apex aneurysm using PulseRider-assistance. Narsinh KH, Caton MT, Mahmood NF, Higashida RT, Halbach VV, Hetts SW, Amans MR, Dowd CF, Cooke DL. Interdiscip Neurosurg. 2021 Jun;24:101072. doi: 10.1016/j.inat.2020.101072. Epub 2020 Dec 29.

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome. Smegal LF, Sebold AJ, Hammill AM, Juhász C, Lo WD, Miles DK, Wilfong AA, Levin AV, Fisher B, Ball KL, Pinto AL, Comi AM; National Institutes of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2021 Jun;119:3-10. doi: 10.1016/j.pediatrneurol.2021.02.006. Epub 2021 Mar 5.

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Wetzel-Strong SE, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.

Vascular malformations are growths composed of blood vessels involving arteries, veins, capillaries, and lymphatics. Patients with vascular malformations in the central nervous system may experience a range of debilitating or life-threatening symptoms including seizures, headaches, and increased risk of cerebral hemorrhage. Due to their inaccessible location, these malformations are difficult to monitor and treat. Therefore, biomarkers from a non-invasive tissue source, such as blood, may aid in predicting disease severity and outcomes. In this study, researchers compared circulating biomarker levels in plasma from patients with sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformations (CCM), and hereditary hemorrhagic telangiectasia (HHT). They found that biomarkers may be unique to each type of vascular malformation, indicating potential usefulness in assessing phenotypic traits of vascular malformations.

Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Thompson KP, Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2021 Jan 6;16(1):12. doi: 10.1186/s13023-020-01579-2.

Quantitative EEG improves prediction of Sturge-Weber syndrome in infants with port-wine birthmark. Gill RE, Tang B, Smegal L, Adamek JH, McAuliffe D, Lakshmanan BM, Srivastava S, Quain AM, Sebold AJ, Lin DDM, Kossoff EH, Caffo B, Comi AM, Ewen JB. Clin Neurophysiol. 2021 Oct;132(10):2440-2446. doi: 10.1016/j.clinph.2021.06.030. Epub 2021 Aug 5.

Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations. Fox CK, Nelson J, McCulloch CE, Weinsheimer S, Pawlikowska L, Hart B, Mabray M, Zafar A, Morrison L, Zabramski JM, Akers A, Kim H. Neurology. 2021 Aug 13;97(12):e1210-6. doi: 10.1212/WNL.0000000000012569. Online ahead of print.

Sirolimus Treatment in Sturge-Weber Syndrome. Sebold AJ, Day AM, Ewen J, Adamek J, Byars A, Cohen B, Kossoff EH, Mizuno T, Ryan M, Sievers J, Smegal L, Suskauer SJ, Thomas C, Vinks A, Zabel TA, Hammill AM, Comi AM. Pediatr Neurol. 2021 Feb;115:29-40. doi: 10.1016/j.pediatrneurol.2020.10.013. Epub 2020 Nov 2.

Systemic and CNS manifestations of inherited cerebrovascular malformations. Hart BL, Mabray MC, Morrison L, Whitehead KJ, Kim H. Clin Imaging. 2021 Jul;75:55-66. doi: 10.1016/j.clinimag.2021.01.020. Epub 2021 Jan 20.

Review paper examines imaging and clinical features of cerebrovascular malformations with a genetic basis, summarizing the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia. Thompson KP, Nelson J, Kim H, Weinsheimer SM, Marchuk DA, Lawton MT, Krings T, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2021 Sep 19;16(1):390. doi: 10.1186/s13023-021-02012-y.

Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture. Copelan A, Drocton G, Caton MT, Smith ER, Cooke DL, Nelson J, Abla AA, Fox C, Amans MR, Dowd CF, Halbach VV, Higashida RT, Lawton MT, Kim H, Fullerton HJ, Gupta N, Hetts SW; UCSF Center For Cerebrovascular Research and UCSF Pediatric Brain Center. Stroke. 2020 Oct;51(10):2990-2996. doi: 10.1161/STROKEAHA.120.030135. Epub 2020 Sep 11.

Clinical outcomes after revascularization for pediatric moyamoya disease and syndrome: A single-center series. Morshed RA, Abla AA, Murph D, Dao JM, Winkler EA, Burkhardt JK, Colao K, Hetts SW, Fullerton HJ, Lawton MT, Gupta N, Fox CK. J Clin Neurosci. 2020 Sep;79:137-143. doi: 10.1016/j.jocn.2020.07.016. Epub 2020 Aug 19.

Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome. Isikbay M, Narsinh KH, Arroyo S, Smith WS, Cooke DL, Higashida RT, Amans MR. J Vasc Surg Cases Innov Tech. 2020 Oct 27;7(1):171-175. doi: 10.1016/j.jvscit.2020.10.010. eCollection 2021 Mar.

Cutaneous findings of familial cerebral cavernous malformation syndrome due to the common Hispanic mutation. Manole AK, Forrester VJ, Zlotoff BJ, Hart BL, Morrison LA. Am J Med Genet A. 2020 May;182(5):1066-1072. doi: 10.1002/ajmg.a.61519. Epub 2020 Feb 26.

Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial. Mabray MC, Caprihan A, Nelson J, McCulloch CE, Zafar A, Kim H, Hart BL, Morrison L. Transl Stroke Res. 2020 Jun;11(3):319-321. doi: 10.1007/s12975-019-00737-4. Epub 2019 Oct 23.

Genome-wide Genotyping of Cerebral Cavernous Malformation Type 1 Individuals to Identify Genetic Modifiers of Disease Severity. Choquet H, Kim H. Methods Mol Biol. 2020;2152:77-84. doi: 10.1007/978-1-0716-0640-7_6.

Genotype-Phenotype Correlations in Children with HHT. Kilian A, Latino GA, White AJ, Clark D, Chakinala MM, Ratjen F, McDonald J, Whitehead K, Gossage JR, Lin D, Henderson K, Pollak J, McWilliams JP, Kim H, Lawton MT, Faughnan ME; the Brain Vascular Malformation Consortium HHT Investigator Group. J Clin Med. 2020 Aug 22;9(9):2714. doi: 10.3390/jcm9092714.

High Prevalence of Spinal Cord Cavernous Malformations in the Familial Cerebral Cavernous Malformations Type 1 Cohort. Mabray MC, Starcevich J, Hallstrom J, Robinson M, Bartlett M, Nelson J, Zafar A, Kim H, Morrison L, Hart BL. AJNR Am J Neuroradiol. 2020 Jun;41(6):1126-1130. doi: 10.3174/ajnr.A6584. Epub 2020 May 28.

Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs. Narsinh KH, Mueller K, Nelson J, Massachi J, Murph DC, Copelan AZ, Hetts SW, Halbach VV, Higashida RT, Abla AA, Amans MR, Dowd CF, Kim H, Cooke DL. AJNR Am J Neuroradiol. 2020 Dec;41(12):2303-2310. doi: 10.3174/ajnr.A6846. Epub 2020 Oct 29.

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia. Cannavicci A, Zhang Q, Kutryk MJB. J Clin Med. 2020 Oct 17;9(10):3333. doi: 10.3390/jcm9103333.

Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA. Nat Commun. 2020 May 27;11(1):2659. doi: 10.1038/s41467-020-16436-w.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software. Copelan AZ, Smith ER, Drocton GT, Narsinh KH, Murph D, Khangura RS, Hartley ZJ, Abla AA, Dillon WP, Dowd CF, Higashida RT, Halbach VV, Hetts SW, Cooke DL, Keenan K, Nelson J, Mccoy D, Ciano M, Amans MR. AJNR Am J Neuroradiol. 2020 Dec;41(12):2235-2242. doi: 10.3174/ajnr.A6908. Epub 2020 Nov 19.

Subjective Cognitive Concerns and Attitudes toward Genetic Testing Are Associated with Depressive Symptoms and Quality of Life after Genetic Testing for the Cerebral Cavernous Malformation Common Hispanic Mutation (CCM1). Campbell R, Petranovich CL, Cheek S, Morrison L, Hart B. J Behav Brain Sci. 2020 Feb;10(2):118-127. doi: 10.4236/jbbs.2020.102007. Epub 2020 Feb 25.

The Expanding Cell Diversity of the Brain Vasculature. Ross JM, Kim C, Allen D, Crouch EE, Narsinh K, Cooke DL, Abla AA, Nowakowski TJ, Winkler EA. Front Physiol. 2020 Dec 3;11:600767. doi: 10.3389/fphys.2020.600767. eCollection 2020.

Vertebral Intraosseous Vascular Malformations in a Familial Cerebral Cavernous Malformation Population: Prevalence, Histologic Features, and Associations With CNS Disease. Tandberg SR, Bocklage T, Bartlett MR, Morrison LA, Nelson J, Hart BL. AJR Am J Roentgenol. 2020 Feb;214(2):428-436. doi: 10.2214/AJR.19.21492. Epub 2019 Dec 11.

A theory for polymicrogyria and brain arteriovenous malformations in HHT. Klostranec JM, Chen L, Mathur S, McDonald J, Faughnan ME, Ratjen F, Krings T. Neurology. 2019 Jan 1;92(1):34-42. doi: 10.1212/WNL.0000000000006686.

Angiopoietin-2 predicts morbidity in adults with Fontan physiology. Shirali AS, Lluri G, Guihard PJ, Conrad MB, Kim H, Pawlikowska L, Boström KI, Iruela-Arispe ML, Aboulhosn JA. Sci Rep. 2019 Dec 4;9(1):18328. doi: 10.1038/s41598-019-54776-w.

Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia (1). Cannavicci A, Zhang Q, Dai SC, Faughnan ME, Kutryk MJB. Can J Physiol Pharmacol. 2019 Jun;97(6):562-569. doi: 10.1139/cjpp-2018-0508. Epub 2018 Dec 4.

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. Tang AT, Sullivan KR, Hong CC, Goddard LM, Mahadevan A, Ren A, Pardo H, Peiper A, Griffin E, Tanes C, Mattei LM, Yang J, Li L, Mericko-Ishizuka P, Shen L, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Roedel CJ, Li N, Zhu Q, Whitehead KJ, Zheng X, Akers A, Morrison L, Kim H, Bittinger K, Lengner CJ, Schwaninger M, Velcich A, Augenlicht L, Abdelilah-Seyfried S, Min W, Marchuk DA, Awad IA, Kahn ML. Sci Transl Med. 2019 Nov 27;11(520):eaaw3521. doi: 10.1126/scitranslmed.aaw3521.

Familial Cerebral Cavernous Malformations. Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL, Mabray MC, Vigil C, Tang AT, Kahn ML, Yonas H, Lawton MT, Kim H, Morrison L. Stroke. 2019 May;50(5):1294-1301. doi: 10.1161/STROKEAHA.118.022314.

Gαq and hyper-phosphorylated ERK expression in Sturge-Weber syndrome leptomeningeal blood vessel endothelial cells. Wellman RJ, Cho SB, Singh P, Tune M, Pardo CA, Comi AM; BVMC Sturge–Weber syndrome Project Workgroup. Vasc Med. 2019 Feb;24(1):72-75. doi: 10.1177/1358863X18786068. Epub 2018 Aug 16.

Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset. Day AM, Hammill AM, Juhász C, Pinto AL, Roach ES, McCulloch CE, Comi AM; National Institutes of Health Sponsor: Rare Diseases Clinical Research Network (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2019 Jan;90:8-12. doi: 10.1016/j.pediatrneurol.2018.04.009. Epub 2018 Nov 24.

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome. Day AM, McCulloch CE, Hammill AM, Juhász C, Lo WD, Pinto AL, Miles DK, Fisher BJ, Ball KL, Wilfong AA, Levin AV, Thau AJ, Comi AM; National Institute of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group, Koenig JI, Lawton MT, Marchuk DA, Moses MA, Freedman SF, Pevsner J. Pediatr Neurol. 2019 Jul;96:30-36. doi: 10.1016/j.pediatrneurol.2018.12.002. Epub 2018 Dec 20.

Quality of Life in Children With Sturge-Weber Syndrome. Harmon KA, Day AM, Hammill AM, Pinto AL, McCulloch CE, Comi AM; National Institutes of Health Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Pediatr Neurol. 2019 Dec;101:26-32. doi: 10.1016/j.pediatrneurol.2019.04.004. Epub 2019 Apr 24.

Sturge-Weber Syndrome Patient Registry: Delayed Diagnosis and Poor Seizure Control. Cho S, Maharathi B, Ball KL, Loeb JA, Pevsner J. J Pediatr. 2019 Dec;215:158-163.e6. doi: 10.1016/j.jpeds.2019.08.025. Epub 2019 Oct 3.

A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. De la Torre AJ, Luat AF, Juhász C, Ho ML, Argersinger DP, Cavuoto KM, Enriquez-Algeciras M, Tikkanen S, North P, Burkhart CN, Chugani HT, Ball KL, Pinto AL, Loeb JA. Pediatr Neurol. 2018 Jul;84:11-20. doi: 10.1016/j.pediatrneurol.2018.04.005. Epub 2018 Apr 18.

A user-guided tool for semi-automated cerebral microbleed detection and volume segmentation: Evaluating vascular injury and data labelling for machine learning. Morrison MA, Payabvash S, Chen Y, Avadiappan S, Shah M, Zou X, Hess CP, Lupo JM. Neuroimage Clin. 2018 Aug 4;20:498-505. doi: 10.1016/j.nicl.2018.08.002. eCollection 2018.

Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia. Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Mol Genet Genomic Med. 2018 May;6(3):350-356. doi: 10.1002/mgg3.377. Epub 2018 Mar 6.

Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing. Walcott BP, Winkler EA, Zhou S, Birk H, Guo D, Koch MJ, Stapleton CJ, Spiegelman D, Dionne-Laporte A, Dion PA, Kahle KT, Rouleau GA, Lawton MT. Hum Genome Var. 2018 Mar 8;5:18001. doi: 10.1038/hgv.2018.1. eCollection 2018.

Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study. Meybodi AT, Kim H, Nelson J, Hetts SW, Krings T, terBrugge KG, Faughnan ME, Lawton MT; Brain Vascular Malformation Consortium HHT Investigator Group. Neurosurgery. 2018 Jan 1;82(1):35-47. doi: 10.1093/neuros/nyx168.

Arterial Ischemic Stroke in Children and Young Adults. Lo WD, Kumar R. Continuum (Minneap Minn). 2017 Feb;23(1, Cerebrovascular Disease):158-180. doi: 10.1212/CON.0000000000000438.

Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Zou X, Hart BL, Mabray M, Bartlett MR, Bian W, Nelson J, Morrison LA, McCulloch CE, Hess CP, Lupo JM, Kim H. Neuroradiology. 2017 Jul;59(7):685-690. doi: 10.1007/s00234-017-1845-8. Epub 2017 May 22.

Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N, Girard R, Zeineddine HA, Lightle R, Moore T, Cao Y, Shenkar R, Chen M, Mericko P, Yang J, Li L, Tanes C, Kobuley D, Võsa U, Whitehead KJ, Li DY, Franke L, Hart B, Schwaninger M, Henao-Mejia J, Morrison L, Kim H, Awad IA, Zheng X, Kahn ML. Nature. 2017 May 18;545(7654):305-310. doi: 10.1038/nature22075. Epub 2017 May 10.

Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome. Pilli VK, Chugani HT, Juhász C. Neurology. 2017 Jan 3;88(1):103-105. doi: 10.1212/WNL.0000000000003455. Epub 2016 Nov 18.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Strickland CD, Eberhardt SC, Bartlett MR, Nelson J, Kim H, Morrison LA, Hart BL. Radiology. 2017 Aug;284(2):443-450. doi: 10.1148/radiol.2017161127. Epub 2017 Mar 20.

Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia. Kasthuri RS, Montifar M, Nelson J, Kim H, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Am J Hematol. 2017 Jun 22:10.1002/ajh.24832. doi: 10.1002/ajh.24832. Online ahead of print.

Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome. Offermann EA, Sreenivasan A, DeJong MR, Lin DDM, McCulloch CE, Chung MG, Comi AM; National Institute of Health Sponsor; Rare Disease Clinical Research Consortium (RDCRN); Brain and Vascular Malformation Consortium (BVMC); National Sturge-Weber Syndrome Workgroup. Pediatr Neurol. 2017 Sep;74:15-23.e5. doi: 10.1016/j.pediatrneurol.2017.04.026. Epub 2017 May 8.

Size of Facial Port-Wine Birthmark May Predict Neurologic Outcome in Sturge-Weber Syndrome. Dymerska M, Kirkorian AY, Offermann EA, Lin DD, Comi AM, Cohen BA. J Pediatr. 2017 Sep;188:205-209.e1. doi: 10.1016/j.jpeds.2017.05.053. Epub 2017 Jul 12.

Anticonvulsant Efficacy in Sturge-Weber Syndrome. Kaplan EH, Kossoff EH, Bachur CD, Gholston M, Hahn J, Widlus M, Comi AM. Pediatr Neurol. 2016 May;58:31-6. doi: 10.1016/j.pediatrneurol.2015.10.015. Epub 2016 Jan 11.

Brainstem cavernous malformations: Natural history versus surgical management. Walcott BP, Choudhri O, Lawton MT. J Clin Neurosci. 2016 Oct;32:164-5. doi: 10.1016/j.jocn.2016.03.021. Epub 2016 Jun 16.

Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1. Choquet H, Trapani E, Goitre L, Trabalzini L, Akers A, Fontanella M, Hart BL, Morrison LA, Pawlikowska L, Kim H, Retta SF. Free Radic Biol Med. 2016 Mar;92:100-109. doi: 10.1016/j.freeradbiomed.2016.01.008. Epub 2016 Jan 19.

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research. Comi AM, Sahin M, Hammill A, Kaplan EH, Juhász C, North P, Ball KL, Levin AV, Cohen B, Morris J, Lo W, Roach ES; 2015 Sturge-Weber Syndrome Research Workshop. Pediatr Neurol. 2016 May;58:12-24. doi: 10.1016/j.pediatrneurol.2015.11.009. Epub 2016 Mar 16.

Molecular, Cellular, and Genetic Determinants of Sporadic Brain Arteriovenous Malformations. Walcott BP, Winkler EA, Rouleau GA, Lawton MT. Neurosurgery. 2016 Aug;63 Suppl 1(Suppl 1 CLINICAL NEUROSURGERY):37-42. doi: 10.1227/NEU.0000000000001300.

Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms. Walcott BP, Reinshagen C, Stapleton CJ, Choudhri O, Rayz V, Saloner D, Lawton MT. J Cereb Blood Flow Metab. 2016 Jun;36(6):998-1003. doi: 10.1177/0271678X16641125. Epub 2016 Mar 23.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

[Formula: see text]Intellectual and adaptive functioning in Sturge-Weber Syndrome. Kavanaugh B, Sreenivasan A, Bachur C, Papazoglou A, Comi A, Zabel TA. Child Neuropsychol. 2016;22(6):635-48. doi: 10.1080/09297049.2015.1028349. Epub 2015 May 8.

Armies of pestilence: CNS infections as potential weapons of mass destruction. Hart BL, Ketai L. AJNR Am J Neuroradiol. 2015 Jun;36(6):1018-25. doi: 10.3174/ajnr.A4177. Epub 2014 Dec 4.

Current Therapeutic Options in Sturge-Weber Syndrome. Comi A. Semin Pediatr Neurol. 2015 Dec;22(4):295-301. doi: 10.1016/j.spen.2015.10.005. Epub 2015 Nov 11.

Genetics of cerebral cavernous malformations: current status and future prospects. Choquet H, Pawlikowska L, Lawton MT, Kim H. J Neurosurg Sci. 2015 Sep;59(3):211-20. Epub 2015 Apr 22.

Hemorrhage rates from brain arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia. Kim H, Nelson J, Krings T, terBrugge KG, McCulloch CE, Lawton MT, Young WL, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Stroke. 2015 May;46(5):1362-4. doi: 10.1161/STROKEAHA.114.007367. Epub 2015 Apr 9.

Increased number of white matter lesions in patients with familial cerebral cavernous malformations. Golden MJ, Morrison LA, Kim H, Hart BL. AJNR Am J Neuroradiol. 2015 May;36(5):899-903. doi: 10.3174/ajnr.A4200. Epub 2015 Jan 2.

Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations. Krings T, Kim H, Power S, Nelson J, Faughnan ME, Young WL, terBrugge KG; Brain Vascular Malformation Consortium HHT Investigator Group. AJNR Am J Neuroradiol. 2015 May;36(5):863-70. doi: 10.3174/ajnr.A4210. Epub 2015 Jan 8.

Sensitivity of patients with familial cerebral cavernous malformations to therapeutic radiation. Golden M, Saeidi S, Liem B, Marchand E, Morrison L, Hart B. J Med Imaging Radiat Oncol. 2015 Feb;59(1):134-6. doi: 10.1111/1754-9485.12269. Epub 2015 Jan 7.

Sturge-Weber syndrome. Comi AM. Handb Clin Neurol. 2015;132:157-68. doi: 10.1016/B978-0-444-62702-5.00011-1.

The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with ENG mutations, but not in patients with ACVRL1 mutations. Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Young WL, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Am J Med Genet A. 2015 Jun;167(6):1262-7. doi: 10.1002/ajmg.a.36936. Epub 2015 Apr 2.

Association of cardiovascular risk factors with disease severity in cerebral cavernous malformation type 1 subjects with the common Hispanic mutation. Choquet H, Nelson J, Pawlikowska L, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H. Cerebrovasc Dis. 2014;37(1):57-63. doi: 10.1159/000356839. Epub 2013 Dec 21.

Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. Cheng KH, Mariampillai A, Lee KK, Vuong B, Luk TW, Ramjist J, Curtis A, Jakubovic H, Kertes P, Letarte M, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group, Yang VX. J Biomed Opt. 2014 Aug;19(8):086015. doi: 10.1117/1.JBO.19.8.086015.

Polymorphisms in inflammatory and immune response genes associated with cerebral cavernous malformation type 1 severity. Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study. Cerebrovasc Dis. 2014;38(6):433-40. doi: 10.1159/000369200. Epub 2014 Dec 3.

Preliminary reliability and validity of a battery for assessing functional skills in children with Sturge-Weber syndrome. Reidy TG, Suskauer SJ, Bachur CD, McCulloch CE, Comi AM. Childs Nerv Syst. 2014 Dec;30(12):2027-36. doi: 10.1007/s00381-014-2573-6. Epub 2014 Oct 26.

Severity score for hereditary hemorrhagic telangiectasia. Latino GA, Kim H, Nelson J, Pawlikowska L, Young W, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Orphanet J Rare Dis. 2014 Dec 29;9:188. doi: 10.1186/s13023-014-0188-3.

Stimulant use in patients with sturge-weber syndrome: safety and efficacy. Lance EI, Lanier KE, Zabel TA, Comi AM. Pediatr Neurol. 2014 Nov;51(5):675-80. doi: 10.1016/j.pediatrneurol.2013.11.009. Epub 2013 Nov 21.

Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. Lance EI, Sreenivasan AK, Zabel TA, Kossoff EH, Comi AM. J Child Neurol. 2013 Feb;28(2):213-8. doi: 10.1177/0883073812463607. Epub 2012 Oct 30.

Brain Vascular Malformation Consortium: Overview, Progress and Future Directions. Akers AL, Ball KL, Clancy M, Comi AM, Faughnan ME, Gopal-Srivastava R, Jacobs TP, Kim H, Krischer J, Marchuk DA, McCulloch CE, Morrison L, Moses M, Moy CS, Pawlikowska L, Young WL. J Rare Disord. 2013 Apr 1;1(1):5.

Case report of subdural hematoma in a patient with Sturge-Weber syndrome and literature review: questions and implications for therapy. Lopez J, Yeom KW, Comi A, Van Haren K. J Child Neurol. 2013 May;28(5):672-5. doi: 10.1177/0883073812449514. Epub 2012 Jul 17.

Dynamic contrast-enhanced MRI evaluation of cerebral cavernous malformations. Hart BL, Taheri S, Rosenberg GA, Morrison LA. Transl Stroke Res. 2013 Oct;4(5):500-6. doi: 10.1007/s12975-013-0285-y. Epub 2013 Sep 21.

Importance of utilizing a sensitive free thyroxine assay in Sturge-Weber syndrome. Siddique L, Sreenivasan A, Comi AM, Germain-Lee EL. J Child Neurol. 2013 Feb;28(2):269-74. doi: 10.1177/0883073812463606. Epub 2012 Oct 30.

Increased choroidal thickness in patients with Sturge-Weber syndrome. Arora KS, Quigley HA, Comi AM, Miller RB, Jampel HD. JAMA Ophthalmol. 2013 Sep;131(9):1216-9. doi: 10.1001/jamaophthalmol.2013.4044.

Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. N Engl J Med. 2013 May 23;368(21):1971-9. doi: 10.1056/NEJMoa1213507. Epub 2013 May 8.

Sturge-weber syndrome. Bachur CD, Comi AM. Curr Treat Options Neurol. 2013 Oct;15(5):607-17. doi: 10.1007/s11940-013-0253-6.

Urine vascular biomarkers in Sturge-Weber syndrome. Sreenivasan AK, Bachur CD, Lanier KE, Curatolo AS, Connors SM, Moses MA, Comi AM. Vasc Med. 2013 Jun;18(3):122-8. doi: 10.1177/1358863X13486312.

Brain arteriovenous malformation multiplicity predicts the diagnosis of hereditary hemorrhagic telangiectasia: quantitative assessment. Bharatha A, Faughnan ME, Kim H, Pourmohamad T, Krings T, Bayrak-Toydemir P, Pawlikowska L, McCulloch CE, Lawton MT, Dowd CF, Young WL, Terbrugge KG. Stroke. 2012 Jan;43(1):72-8. doi: 10.1161/STROKEAHA.111.629865. Epub 2011 Oct 27.

Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schrum SD, James M, Quinnine N, Bharatha A, Terbrugge KG, White RI Jr. Am J Med Genet A. 2012 Nov;158A(11):2829-34. doi: 10.1002/ajmg.a.35622. Epub 2012 Sep 18.

Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Lo W, Marchuk DA, Ball KL, Juhász C, Jordan LC, Ewen JB, Comi A; Brain Vascular Malformation Consortium National Sturge-Weber Syndrome Workgroup. Dev Med Child Neurol. 2012 Mar;54(3):214-23. doi: 10.1111/j.1469-8749.2011.04169.x. Epub 2011 Dec 23.

Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Comi AM. Neurologist. 2011 Jul;17(4):179-84. doi: 10.1097/NRL.0b013e318220c5b6.

Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype. Petersen TA, Morrison LA, Schrader RM, Hart BL. AJNR Am J Neuroradiol. 2010 Feb;31(2):377-82. doi: 10.3174/ajnr.A1822. Epub 2009 Oct 15.

Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta. Liu W, Nicol L, Orwoll E. Calcif Tissue Int. 2024 Mar 12. doi: 10.1007/s00223-024-01188-2. Epub ahead of print. PMID: 38472351.

Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Drugs to improve skeletal health—including those initially developed to treat osteoporosis as well as new bone-protective agents—are in various phases of clinical trials for adults with OI.

In this review article, researchers summarize current and developing pharmacologic agents for improving skeletal health in adults with OI. The team performed online database searches to review published studies and clinical trials.

Results include ongoing clinical trials for several therapeutics, including those that may be useful in improving bone mineral density. Authors note that clinical trials involving gene editing may be possible in the coming decade.

Psychosocial Outcomes of Pain and Pain Management in Adults with Osteogenesis Imperfecta: A Qualitative Study. Shepherd WS, Wiese AD, Cho HE, Rork WC, Baig MU, Kostick KM, Nguyen D, Carter EM; Members of the BBDC; Murali CN, Robinson ME, Schneider SC, Lee B, Sutton VR, Storch EA. J Clin Psychol Med Settings. 2024 Jan 28. doi: 10.1007/s10880-023-09991-z. Epub ahead of print. PMID: 38281305.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures. Symptoms include short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Although research on the functional outcomes of OI is growing, few studies are examining the psychosocial outcomes of pain in OI.

In this study, researchers interviewed 15 adults with OI to understand pain-related experiences. First, the team developed an interview guide focused on topics related to pain and mental health challenges. Next, the team interviewed participants and analyzed transcripts to identify common themes.

Results show that participants experience chronic and acute pain related to OI. Pharmacological treatments were the most common pain management approach. Participants reported negative pain outcomes, including limited daily functioning and activity participation, fear, anger, anxiety, depression, and difficulty concentrating. Participants also suggested that lack of physician and community knowledge on chronic pain in OI indirectly exacerbates both subjective pain intensity and outcomes.

Authors note that this study provides valuable exploration of the unique pain experiences of adults with OI that may have implications for proactive management, treatment development, and clinician training.

A qualitative exploration of patient perspectives on psychosocial burdens and positive factors in adults with osteogenesis imperfecta. Rork WC, Hertz AG, Wiese AD, Kostick KM, Nguyen D, Schneider SC, Shepherd WS, Cho H; Members of the BBDC; Murali CN, Lee B, Sutton VR, Storch EA. Am J Med Genet A. 2023 Sep;191(9):2267-2275. doi: 10.1002/ajmg.a.63323. Epub 2023 Jun 15. PMID: 37317786

Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Although progress has been made in understanding the spectrum of physical symptoms, less is known about the impact of OI on psychosocial well-being, as well as factors that can help lessen negative outcomes.

In this study, researchers developed a qualitative approach to assess perspectives from individuals with OI on psychosocial burdens and positive factors related to OI. Among 15 adults with varying disease status, the team conducted semi-structured interviews and identified themes from responses.

Participants reported negative psychosocial outcomes related to bone fractures and recovery, uncertainty of future fractures, and self-image. Participants also described positive traits related to OI and their lived experience with a chronic disease. Authors note that these insights highlight a need for continued research on the relationship between OI disease status and psychosocial outcomes, as well as the development of psychological interventions designed for individuals with OI.

Approach to the Patient: Pharmacological therapies for fracture risk reduction in adults with osteogenesis imperfecta. Liu W, Lee B, Nagamani SCS, Nicol L, Rauch F, Rush ET, Sutton VR, Orwoll E. J Clin Endocrinol Metab. 2023 Jan 20:dgad035. doi: 10.1210/clinem/dgad035. Epub ahead of print. PMID: 36658750.

Osteogenesis imperfecta (OI) is a group of 21 rare, inherited disorders caused by 19 gene mutations resulting in fragile bones that break easily. The effectiveness of medications used for fracture reduction in adults with OI, as well as practice recommendations, are not well established.

In this review paper, researchers summarize current knowledge on pharmacologic treatment options for reducing fracture risk in adults with OI. In addition to manual searches of reference lists, the team performed a PubMed online database search of all study types published in the English language using the terms “osteogenesis imperfecta,” “OI,” and “brittle bone disease.”

Findings show that despite limited clinical trial data, bisphosphonate and teriparatide therapies may help improve bone mineral density in adults with OI. Authors state that further research is needed to develop medications for adults with OI that will lead to definite fracture rate reduction.

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta. Rodriguez Celin M, Kruger KM, Caudill A, Murali CN, Nagamani SCS, Members Of The Brittle Bone Disorders Consortium Bbdc, Smith PA, Harris GF. Am J Med Genet A. 2022 Oct 22. doi: 10.1002/ajmg.a.63009. Epub ahead of print. PMID: 36271817.

Osteogenesis imperfecta (OI) is a group of rare, inherited disorders caused by gene mutations resulting in fragile bones that break easily. Symptoms include skeletal and joint deformities, hearing loss, a bluish tint to the sclerae (whites of the eyes), dental problems, respiratory problems, and chronic pain. In this study, researchers aimed to describe pain characteristics and treatments used in individuals with varying severity of OI, as well as investigate variables associated with pain. Using data from a natural history study of OI conducted by the Brittle Bone Disorders Consortium (BBDC), the team analyzed the prevalence, characteristics, treatments, and predictors of chronic pain. Among 861 individuals with OI, results showed that 41.8% had chronic pain, which was most frequently located in the back. Predictors of chronic pain for all OI types included age, use of a wheelchair, and number of fractures per year. Compared to participants without chronic pain, participants with chronic pain missed more days from school or work per year and performed worse in all mobility metrics. The most common treatments were nonsteroidal anti-inflammatory drugs and bisphosphonates. These results show that chronic pain is prevalent in OI across all types, affects mobility, and interferes with participation.

Targeting TGF-β for treatment of osteogenesis imperfecta. Song IW, Nagamani SC, Nguyen D, Grafe I, Sutton VR, Gannon FH, Munivez E, Jiang MM, Tran A, Wallace M, Esposito P, Musaad S, Strudthoff E, McGuire S, Thornton M, Shenava V, Rosenfeld S, Huang S, Shypailo R, Orwoll E, Lee B. J Clin Invest. 2022 Apr 1;132(7):e152571. doi: 10.1172/JCI152571.

Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta. Nicol LE, Coghlan RF, Cuthbertson D, Nagamani SCS, Lee B, Olney RC, Horton W; Members of the Brittle Bone Disease Consortium, Orwoll E. Bone. 2021 Aug;149:115990. doi: 10.1016/j.bone.2021.115990. Epub 2021 Apr 28.

Osteogenesis imperfecta is a genetic disorder characterized by bone fragility, abnormal bone growth, and short stature. In this study, researchers sought to better understand the mechanisms by which abnormalities in collagen contribute to growth plate dysfunction. Growth plates are the areas of new bone growth in children and teens, which are made up of cartilage. Researchers examined the presence of Type X collagen (CXM), which has been found to be a reliable marker for new bone formation in cartilage, in blood samples of 187 subjects ages 8 months to 40 years with OI compared with control subjects. All subjects had higher levels of CXM early in life and during puberty, but there was greater variability for the OI cohort and a weaker relationship with growth velocity. The ratio of CXM level to growth velocity was elevated in children with type III/IV OI compared to controls. Results suggest that the relationship between growth plate and the end point of skeletal growth is disrupted in OI. 

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay. Marom R, Burrage LC, Venditti R, Clément A, Blanco-Sánchez B, Jain M, Scott DA, Rosenfeld JA, Sutton VR, Shinawi M, Mirzaa G, DeVile C, Roberts R, Calder AD, Allgrove J, Grafe I, Lanza DG, Li X, Joeng KS, Lee YC, Song IW, Sliepka JM, Batkovskyte D, Washington M, Dawson BC, Jin Z, Jiang MM, Chen S, Chen Y, Tran AA, Emrick LT, Murdock DR, Hanchard NA, Zapata GE, Mehta NR, Weis MA, Scott AA, Tremp BA, Phillips JB, Wegner J, Taylor-Miller T, Gibbs RA, Muzny DM, Jhangiani SN, Hicks J, Stottmann RW, Dickinson ME, Seavitt JR, Heaney JD, Eyre DR; Undiagnosed Diseases Network, Westerfield M, De Matteis MA, Lee B. Am J Hum Genet. 2021 Sep 2;108(9):1710-1724. doi: 10.1016/j.ajhg.2021.08.002. Epub 2021 Aug 26.

Vesicle coat proteins help cells sort and transport or “traffic” proteins and lipids. Pathogenic variants (mutations) in genes that encode subunits of coat complexes called coatomers are believed to contribute to a number of genetic disorders called coatopathies that can affect the skeletal and central nervous systems. In this study, researchers examined loss-of-function variants in the gene COPB2, which encodes for a protein in the coatomer complex, in six individuals from five unrelated families who have osteoporosis or osteopenia (brittle bones that may fracture easily) and variable degree of developmental delay. Researchers also used zebrafish and mouse models to further study the effect of COPB2 deficiency on collagen trafficking because of the critical role of collagen secretion in bone development. The authors conclude that COPB2 haploinsufficiency (meaning only 50% of the normal active form of a particular protein is expressed) is a cause of this form of coatopathy. They also tested ascorbic acid supplementation as a potential treatment and found that it had a beneficial effect on animal models.

Health-related quality of life in adults with osteogenesis imperfecta. Murali CN, Slater B, Musaad S, Cuthbertson D, Nguyen D, Turner A, Azamian M, Tosi L, Rauch F, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SCS. Clin Genet. 2021 Jun;99(6):772-779. doi: 10.1111/cge.13939. Epub 2021 Feb 22.

Missing and unerupted teeth in osteogenesis imperfecta. Taqi D, Moussa H, Schwinghamer T, Vieira AR, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC. Bone. 2021 Sep;150:116011. doi: 10.1016/j.bone.2021.116011. Epub 2021 May 18.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and craniofacial and dental abnormalities. It is believed that OI patients have missing or unerupted teeth at a rate twice the general population. To better understand the factors influencing missing and unerupted teeth, researchers studied 144 OI patients. They examined clinical phenotype (OI type), the genetic variant type, the tooth type and the onset of biophosphonate treatment, which slows bone loss. They found that the presence of missing and unerupted teeth varied according to the nature of the collagen variants and OI type. These findings highlight the role of collagen in tooth development and eruption.

Osteogenesis imperfecta tooth level phenotype analysis: Cross-sectional study. Taqi D, Moussa H, Schwinghamer T, Ducret M, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC. Bone. 2021 Jun;147:115917. doi: 10.1016/j.bone.2021.115917. Epub 2021 Mar 16.

Pregnancy in women with osteogenesis imperfecta: pregnancy characteristics, maternal, and neonatal outcomes. Rao R, Cuthbertson D, Nagamani SCS, Sutton VR, Lee BH, Krischer J, Krakow D. Am J Obstet Gynecol MFM. 2021 Jul;3(4):100362. doi: 10.1016/j.ajogmf.2021.100362. Epub 2021 Mar 26.

Women with rare diseases considering pregnancy often lack data regarding outcomes, specific risks, and management strategies. The Brittle Bone Disorders Consortium established an Osteogenesis Imperfecta Pregnancy Registry to collect data on pregnancy, maternal, and neonatal outcomes in women with osteogenesis imperfecta (OI), or brittle bone disease. A total of 132 participants with OI completed a cross-sectional, survey-based study. Of respondents, 34% had moderate to severe OI. Researchers compared self-reported information on pregnancy and maternal and neonatal outcomes of women with OI with data on the general population, referenced by literature-based standards. Results indicated that women with OI had higher rates than the general population of diabetes in pregnancy, cesarean delivery, need for blood transfusion, and fractures before or after delivery. Individuals with moderate or severe OI reported higher maternal hospitalization and delivery rates than those with mild OI. Babies born to women with OI had higher rates of neonatal intensive care unit admissions and higher neonatal mortality, regardless of neonatal OI status. Study authors say that patients and providers should be aware of these findings, particularly the need for blood products (hemorrhage) and the increased rate of fractures, low birthweight infants, and neonatal mortality. They suggest that survey results can support both preconception counseling and proactive measures to reduce harm and recognize modifiable risk factors related to pregnancy.

A Multicenter Study of Intramedullary Rodding in Osteogenesis Imperfecta. Rodriguez Celin M, Kruger KM, Caudill A, Nagamani SCS; Brittle Bone Disorders Consortium (BBDC); Linked Clinical Research Centers (LCRC), Harris GF, Smith PA. JB JS Open Access. 2020 Sep 11;5(3):e20.00031. doi: 10.2106/JBJS.OA.20.00031. eCollection 2020 Jul-Sep.

Assessment of longitudinal bone growth in osteogenesis imperfecta using metacarpophalangeal pattern profiles. Rauch D, Robinson ME, Seiltgens C, Sutton VR, Lee B, Glorieux F, Rauch F. Bone. 2020 Nov;140:115547. doi: 10.1016/j.bone.2020.115547. Epub 2020 Jul 27.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study. Machol K, Hadley TD, Schmidt J, Cuthbertson D, Traboulsi H, Silva RC, Citron C, Khan S, Citron K, Carter E, Brookler K, Shapiro JR, Steiner RD, Byers PH, Glorieux FH, Durigova M, Smith P, Bober MB, Sutton VR, Lee BH; Members of the BBD Consortium, Nagamani SCS, Raggio C. Am J Med Genet A. 2020 Apr;182(4):697-704. doi: 10.1002/ajmg.a.61464. Epub 2019 Dec 26.

Malocclusion traits and oral health-related quality of life in children with osteogenesis imperfecta: A cross-sectional study. Najirad M, Madathil SA, Rauch F, Sutton VR, Lee B, Retrouvey JM; Members of the Brittle Bone Diseases Consortium, Esfandiari S. J Am Dent Assoc. 2020 Jul;151(7):480-490.e2. doi: 10.1016/j.adaj.2020.03.040.

Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta. Murali CN, Cuthbertson D, Slater B, Nguyen D, Turner A, Harris G, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SCS. Genet Med. 2020 Mar;22(3):581-589. doi: 10.1038/s41436-019-0688-6. Epub 2019 Nov 27.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta. Bains JS, Carter EM, Citron KP, Boskey AL, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sliepka JM, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SC, Raggio CL. JBMR Plus. 2019 Jan 7;3(5):e10118. doi: 10.1002/jbm4.10118. eCollection 2019 May.

Assessing Disease Experience across the Life Span for Individuals with Osteogenesis Imperfecta: Challenges and Opportunities for Patient-Reported Outcomes (PROs) Measurement. Tosi LL, Floor MK, Dollar CM, Gillies AP; Members of the Brittle Bone Disease Consortium, Hart TS, Cuthbertson DD, Sutton VR, Krischer JP. Orphanet Journal of Rare Diseases. 2019. 14:23. https://doi.org/10.1186/s13023-019- 1004-x. PMID: 30696467.

Caries Prevalence and Experience in Individuals with Osteogenesis Imperfecta. Ma MS, Najirad M, Taqi D, Retrouvey JM, Tamimi F, Dagdeviren D, Glorieux FH, Lee B, Sutton VR, Rauch F, Esfandiari S. Spec Care Dentist. 2019 Mar;39(2):214-219. Epub 2019 Feb 13. https://doi.org/10.1101/418806. PMID: 30758072.

Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in IFITM5. Dagdeviren D, Tamimi F, Lee B, Sutton R, Rauch F, Retrouvey JM. Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in IFITM5. Dagdeviren D, Tamimi F, Lee B, Sutton V, Rauch F, Retrouvey JM. Am J Med Genet A. 2018 Oct 5. doi: 10.1002/ajmg.a.40383. PMID: 30289614.

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study. Jain M, Tam A, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Mullins M, Bellur S, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Lee B, Sutton VR; , Members of the Brittle Bone Disorders Consortium*, Nagamani SCS. Genet Med. 2018 Jul 4. doi: 10.1038/s41436-018-0045-1. PMID: 29970925.

Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells. Ortinau LC, Wang H, Lei K, Deveza L, Jeong Y, Hara Y, Grafe I, Rosenfeld SB, Lee D, Lee B, Scadden DT, Park D. Cell Stem Cell. 2019 Dec 5;25(6):784-796.e5. doi: 10.1016/j.stem.2019.11.003.

Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community. Swezey T, Reeve BB, Hart TS, Floor MK, Dollar CM, Gillies AP, Tosi LL. Osteoporos Int. 2019 Feb;30(2):507-511. doi: 10.1007/s00198-018-4690-7. Epub 2018 Sep 6. PMID:30191258.

Mobility in Osteogenesis Imperfecta: A Multicenter North American Study. Kruger KM, Caudill A, Rodriguez Celin M, Nagamani SCS, Shapiro JR, Steiner RD, Bober MB, Hart T, Cuthbertson D, Krischer J, Byers PH, Durigova M, Glorieux FH, Rauch F, Sutton VR, Lee B, Rush ET, Smith PA, Harris GF. Genet Med. 2019 Mar 28. doi: 10.1038/s41436-019-0491-4. PMID: 30918359.

Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V. Retrouvey JM, Taqi D, Tamimi F, Dagdeviren D, Glorieux FH, Lee B, Hazboun R, Krakow D, Sutton VR; Members of the BBD Consortium. Eur J Med Genet. 2019 Dec;62(12):103606. doi: 10.1016/j.ejmg.2018.12.011. Epub 2018 Dec 26.

Osteogenesis imperfecta: advancements in genetics and treatment. Rossi V, Lee B, Marom R. Curr Opin Pediatr. 2019 Dec;31(6):708-715. doi: 10.1097/MOP.0000000000000813.

A Multicenter Study to Evaluate Pulmonary Function in Osteogenesis Imperfecta. Tam A, Chen S, Schauer E, Grafe I, Bandi V, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Cuthbertson D, Krischer J, Mullins M, Byers PH, Sandhaus RA, Durigova M, Glorieux FH, Rauch F, Reid Sutton V, Lee B; Members of the Brittle Bone Disorders Consortium, Rush ET, Nagamani SCS. Clin Genet. 2018 Dec;94(6):502-511. doi: 10.1111/cge.13440. Epub 2018 Sep 24. PMID: 30152014.

Cone‐Beam Computed Tomography of Osteogenesis Imperfecta Types III and IV: Three‐Dimensional Evaluation of Craniofacial Features and Upper Airways. Reznikov N, Dagdeviren D, Tamimi F, Glorieux F, Rauch F, Retrouvey JM. JBMR Plus, Epub November 16, 2018; doi: 10.1002/jbm4.10124.

Heterozygous WNT1 variant causing a variable bone phenotype. Alhamdi S, Lee YC, Chowdhury S, Byers PH, Gottschalk M, Taft RJ, Joeng KS, Lee BH, Bird LM. Am J Med Genet A. 2018 Nov;176(11):2419-2424. doi: 10.1002/ajmg.a.40347. Epub 2018 Sep 24.

Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta. Bains JS, Carter EM, Citron KP, Boskey AL, Shapiro JR, Steiner RD, Smith PA, Bober MA, Hart T, Cuthbertson D, Krischer J, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sliepka JM, Sutton VR, Lee B, “Members of the BBD Consortium”, Nagamani SC, Raggio CL. JBMR Plus, Epub October 23, 2018; doi: 10.1002/jbm4.10118.

Oral Health-Related Quality of Life in Children and Adolescents with Osteogenesis Imperfecta: cross- sectional study. Najirad M, Ma MS, Rauch F, Sutton VR, Lee B, Retrouvey JM; Members of the BBD, Esfandiari S. Orphanet J Rare Dis. 2018 Oct 25;13(1):187. doi: https://doi.org/10.1101/424812. PMID: 30359278.

Osteogenesis imperfecta: potential therapeutic approaches. Rousseau M, Retrouvey JM; Members of the Brittle Bone Disease Consortium. PeerJ. 2018 Aug 17;6:e5464. doi: 10.7717/peerj.5464. eCollection 2018. PMID: 30128210.

Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment. Bi X, Grafe I, Ding H, Flores R, Munivez E, Jiang MM, Dawson B, Lee B, Ambrose CG. J Bone Miner Res. 2017 Feb;32(2):347-359. doi: 10.1002/jbmr.2997. Epub 2016 Oct 20.

Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone. Lietman CD, Lim J, Grafe I, Chen Y, Ding H, Bi X, Ambrose CG, Fratzl-Zelman N, Roschger P, Klaushofer K, Wagermaier W, Schmidt I, Fratzl P, Rai J, Weis M, Eyre D, Keene DR, Krakow D, Lee BH. J Bone Miner Res. 2017 Jun;32(6):1354-1367. doi: 10.1002/jbmr.3108. Epub 2017 Mar 20.

Genetic causes and mechanisms of Osteogenesis Imperfecta. Lim J, Grafe I, Alexander S, Lee B. Bone. 2017 Sep;102:40-49. doi: 10.1016/j.bone.2017.02.004. Epub 2017 Feb 15.

Orthodontic chart documentation. Abdelkarim A, Jerrold L. Am J Orthod Dentofacial Orthop. 2017 Jul;152(1):126-130. doi: 10.1016/j.ajodo.2017.03.018.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta. Bellur S, Jain M, Cuthbertson D, Krakow D, Shapiro JR, Steiner RD, Smith PA, Bober MB, Hart T, Krischer J, Mullins M, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Sutton VR, Lee B; Members of the BBD Consortium, Nagamani SC. Genet Med. 2016 Jun;18(6):570-6. doi: 10.1038/gim.2015.131. Epub 2015 Oct 1. PMID: 26426884.

Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta. Grafe I, Alexander S, Yang T, Lietman C, Homan EP, Munivez E, Chen Y, Jiang MM, Bertin T, Dawson B, Asuncion F, Ke HZ, Ominsky MS, Lee B. J Bone Miner Res. 2016 May;31(5):1030-40. doi: 10.1002/jbmr.2776. Epub 2016 Feb 12.

A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation. Lietman CD, Marom R, Munivez E, Bertin TK, Jiang MM, Chen Y, Dawson B, Weis MA, Eyre D, Lee B. J Bone Miner Res. 2015 Mar;30(3):489-98. doi: 10.1002/jbmr.2363.

Analysis of Structural Variants Previously Associated With ALS in Europeans Highlights Genomic Architectural Differences in Africans. Monnakgotla NR, Mahungu AC, Heckmann JM, Botha G, Mulder NJ, Wu G, Rampersaud E, Myers J, Van Blitterswijk M, Rademakers R, Taylor JP, Wuu J, Benatar M, Nel M. Neurol Genet. 2023 Jun 16;9(4):e200077. doi: 10.1212/NXG.0000000000200077. eCollection 2023 Aug.

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study. Kerestes R, Laansma MA, Owens-Walton C, Perry A, van Heese EM, Al-Bachari S, Anderson TJ, Assogna F, Aventurato ÍK, van Balkom TD, Berendse HW, van den Berg KRE, Betts R, Brioschi R, Carr J, Cendes F, Clark LR, Dalrymple-Alford JC, Dirkx MF, Druzgal J, Durrant H, Emsley HCA, Garraux G, Haroon HA, Helmich RC, van den Heuvel OA, João RB, Johansson ME, Khachatryan SG, Lochner C, McMillan CT, Melzer TR, Mosley PE, Newman B, Opriessnig P, Parkes LM, Pellicano C, Piras F, Pitcher TL, Poston KL, Rango M, Roos A, Rummel C, Schmidt R, Schwingenschuh P, Silva LS, Smith V, Squarcina L, Stein DJ, Tavadyan Z, Tsai CC, Vecchio D, Vriend C, Wang JJ, Wiest R, Yasuda CL, Young CB, Jahanshad N, Thompson PM, van der Werf YD, Harding IH; ENIGMA-Parkinson's Study. Mov Disord. 2023 Dec;38(12):2269-2281. doi: 10.1002/mds.29611. Epub 2023 Nov 14.

Racial Differences in Clinical Presentation in Individuals Diagnosed With Frontotemporal Dementia. Jin HA, McMillan CT, Yannatos I, Fisher L, Rhodes E, Jacoby SF, Irwin DJ, Massimo L. JAMA Neurol. 2023 Sep 11:e233093. doi: 10.1001/jamaneurol.2023.3093. Online ahead of print.

Temporal course of cognitive and behavioural changes in motor neuron diseases. McHutchison CA, Wuu J, McMillan CT, Rademakers R, Statland J, Wu G, Rampersaud E, Myers J, Hernandez JP, Abrahams S, Benatar M; CReATe Consortium. J Neurol Neurosurg Psychiatry. 2023 Oct 12:jnnp-2023-331697. doi: 10.1136/jnnp-2023-331697.

While people with motor neuron disease (MND) experience cognitive and behavioral dysfunction, the onset and progression of these symptoms, relative to motor manifestations, remains unclear. In this study, CReATe Consortium researchers explored changes in these deficits over time, and whether demographic, clinical, or genetic factors affected these symptoms.

A total of 237 participants were recruited through the consortium’s Phenotype-Genotype-Biomarker study. The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen was administered every three to six months to assess ALS-specific cognitive issues, such as executive function, verbal fluency, and language; and ALS non-specific memory and visuospatial functions. Behavioral symptoms like apathy, disinhibition, loss of sympathy and perseveration and hyperorality, were reported through semi-structured interviews.

In this large observational study, cognitive impairment at initial assessment was infrequent, but when present, most often involved language and executive functions. These impairments were associated with lower educational levels, but not with the C9ORF72 repeat expansion. We also found that cognition remained stable over time for most patients. However, a small subset showed decline on all cognitive domains, which was not entirely explained by the presence of a C9ORF72 repeat expansion. Behavioral symptoms in these MND participants were uncommon.

Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations. This highlights the need for future research to identify when these cognitive symptoms begin and what other factors are associated with decline over time.

The amyotrophic lateral sclerosis-health index (ALS-HI): development and evaluation of a novel outcome measure. Varma A, Weinstein J, Seabury J, Rosero S, Zizzi C, Alexandrou D, Wagner E, Dilek N, Heatwole J, Wuu J, Caress J, Bedlack R, Granit V, Statland J, Mehta P, Benatar M, Kaat A, Heatwole C. Amyotroph Lateral Scler Frontotemporal Degener. 2023 Aug;24(5-6):514-522. doi: 10.1080/21678421.2023.2204871. Epub 2023 May 15. PMID: 37190795

Amyotrophic lateral sclerosis (ALS) patients experience a wide variety of physical, mental, emotional, and social symptoms of the disease. Tools to track a patient’s subtle but important changes over time are important for managing the disease burden as well as assessing promising new therapeutic agents. Therefore, highly reliable, sensitive, and valid disease-specific outcome measures for ALS are vital for clinicians and researchers, as well as patients and family members.

In this study, the authors report the development of the Amyotrophic Lateral Sclerosis-Health Index (ALS-HI), which was created and validated in accordance with FDA guidance. This is a multifactorial, disease-specific patient-reported outcome measure capable of measuring meaningful changes in how an ALS patient feels and functions.

To develop the ALS-HI, the authors surveyed a national cross section of 497 individuals with ALS. After identifying the most important symptoms of ALS, they performed factor analysis, qualitative patient interviews, test-retest reliability assessment, and known groups analysis to evaluate and validate the ALS-HI. Fifteen participants took part in a beta test and found the ALS-HI to be clear, easy to use, and relevant. 

The study supports use of the ALS-HI as a valid, sensitive, and reliable instrument to assess the disease burden of individual patients with ALS. The ALS-HI could also serve as an effective mechanism to track disease progression and treatment efficacy during therapeutic trials.

The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia. Mahungu AC, Steyn E, Floudiotis N, Wilson LA, Vandrovcova J, Reilly MM, Record CJ, Benatar M, Wu G, Raga S, Wilmshurst JM, Naidu K, Hanna M, Nel M, Heckmann JM. Front Neurol. 2023 Aug 29;14:1239725. doi: 10.3389/fneur.2023.1239725. eCollection 2023.

A rare variant analysis framework using public genotype summary counts to prioritize disease-predisposition genes. Chen W, Wang S, Tithi SS, Ellison DW, Schaid DJ, Wu G. Nat Commun. 2022 May 11;13(1):2592. doi: 10.1038/s41467-022-30248-0.

Adaptation and norming of the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS) for three language groups in South Africa. Albertyn CH, Hardy A, Bakker LA, Hlangani M, Van Der Walt K, Zeilinga B, Thomas KGF, Heckmann JM. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Nov;23(7-8):532-541. doi: 10.1080/21678421.2022.2030361. Epub 2022 Feb 4.

Characteristics of serum neurofilament light chain as a biomarker in hereditary spastic paraplegia type 4. Kessler C, Serna-Higuita LM, Wilke C, Rattay TW, Hengel H, Reichbauer J, Stransky E, Leyva-Gutiérrez A, Mengel D, Synofzik M, Schöls L, Martus P, Schüle R. Ann Clin Transl Neurol. 2022 Mar;9(3):326-338. doi: 10.1002/acn3.51518. Epub 2022 Feb 16. PMID: 35171517; PMCID: PMC8935322.

Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by muscle weakness and tightness (spasticity) in the legs. Easily accessible fluid biomarkers are lacking in spastic paraplegia type 4 (SPG4), the most prevalent form of HSP. In this study, researchers investigated serum neurofilament light chain (sNfL) as a potential therapy response, diagnostic, monitoring, and prognostic biomarker in SPG4. The team assessed sNfL levels in 93 patients with SPG4 and 60 healthy controls. They found that sNfL levels are not suitable to monitor disease progression in SPG4, but may be valuable as a therapy response biomarker. Authors note that because sNfL levels appear to be most dynamic around the onset of SPG4, the ability to detect a therapy response is especially promising in younger patients, matching the need to initiate treatment in early disease stages.

Defining cognitive impairment in amyotrophic lateral sclerosis: an evaluation of empirical approaches. McMillan CT, Wuu J, Rascovsky K, Cosentino S, Grossman M, Elman L, Quinn C, Rosario L, Stark JH, Granit V, Briemberg H, Chenji S, Dionne A, Genge A, Johnston W, Korngut L, Shoesmith C, Zinman L; Canadian ALS Neuroimaging Consortium (CALSNIC), Kalra S, Benatar M. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Mar 7:1-10. doi: 10.1080/21678421.2022.2039713. Online ahead of print.

Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: a new diagnostic entity. Benatar M, Granit V, Andersen PM, Grignon AL, McHutchison C, Cosentino S, Malaspina A, Wuu J. Brain. 2022 May 20:awac185. doi: 10.1093/brain/awac185. Epub ahead of print. PMID: 35594156.

Amyotrophic lateral sclerosis (ALS) is traditionally regarded as a clinical syndrome. Emerging biomarker evidence of disease prior to clinical manifestations of disease, however, have fostered the view that ALS should be considered a biological entity with pre-symptomatic and clinically manifest stages of disease. New data from Pre-fALS, a natural history and biomarker study of people at genetic risk for ALS, now indicate that pre-symptomatic should not necessarily be taken to mean “clinically silent.” Systematic clinical characterization of 20 phenoconverters–pre-symptomatic gene mutation carriers who have been followed from the pre-symptomatic to the clinically manifest stages of disease–reveals evidence of a prodromal state of mild motor impairment (MMI). MMI is characterized by symptoms, signs, or electromyographic findings that represent a departure from normal, but which are insufficiently severe or widespread to clearly indicate ALS. The duration of prodromal MMI varies among carriers of different genetic mutations. Based on these findings, the authors conclude that in three of the most common genetic forms of ALS, MMI is an observable state that is prodromal to clinically manifest disease. The authors hypothesize that this may also be true for all genetic ALS and non-genetic forms of ALS as well. Importantly, MMI is considered both an intermediate (transitional) and an indeterminate state, as not everyone with MMI will progress to develop ALS. As a new diagnostic label, MMI should generate fresh urgency for developing diagnostic biomarkers that might permit earlier therapeutic intervention.

Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers in Primary Progressive Multiple Sclerosis and Hereditary Spastic Paraplegia Type 4. Kessler C, Ruschil C, Abdelhak A, Wilke C, Maleska A, Kuhle J, Krumbholz M, Kowarik MC, Schüle R. Serum. Int J Mol Sci. 2022 Nov 3;23(21):13466. doi: 10.3390/ijms232113466. PMID: 36362248; PMCID: PMC9657281.

Primary progressive multiple sclerosis (PPMS) and hereditary spastic paraplegia (HSP) are inherited disorders affecting nerves that send messages to the muscles. Because patients with both disorders can present with slowly progressive spastic paraparesis (weakness in the legs), accurate diagnoses are often challenging. In this study, researchers investigated the use of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) as biomarkers to support diagnosis. The team assessed sNfl and sGFAP levels in 25 patients with PPMS, 25 patients with spastic paraplegia type 4 (SPG4, the most common type of HSP), and 60 control subjects. Results showed that sNfl levels were significantly higher in patients with PPMS compared to patients with SPG4. Researchers also observed a trend toward relatively higher sGFAP levels in patients with PPMS. However, because both groups of patients showed overlapping biomarker values, the team did not find sNfL and sGFAP to be useful biomarkers. As findings indicate that sNfL and sGFAP are most significantly elevated in the early disease stages of PPMS, authors note that further investigation is warranted.

Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal. Benatar M, Wuu J, Turner MR. Brain. 2022 Oct 31:awac394. doi: 10.1093/brain/awac394. Epub ahead of print. PMID: 36310538.

Interest in amyotrophic lateral sclerosis (ALS) biomarkers has grown exponentially over the course of the last 25 years, with great hope that they might serve as tools to facilitate the development of meaningful therapies for this otherwise progressive and fatal disease. Effective use of biomarkers, however, requires an understanding of what it means for them to be “fit-for-purpose,” as well as an appreciation of the nuances of the clinical contexts in which they will be applied. Neurofilament light chain (NfL) has emerged as a leading candidate with enormous potential to aid ALS therapy development. However, Nfl is also profoundly misunderstood. Within the conceptual framework of the BEST (Biomarkers, EndpointS, and other Tools) Resource developed by the National Institutes of Health and the Food & Drug Administration in the United States, authors consider the evidence supporting the use of NfL for a variety of purposes in different clinical contexts. Authors conclude that NfL may serve as a susceptibility/risk biomarker in populations at elevated risk for ALS, and that NfL has value as a prognostic biomarker when measured early in the course of established disease. Authors also conclude that NfL may serve as a pharmacodynamic biomarker, as a reduction in NfL in response to an experimental therapeutic might aid go/no-go decisions in phase 2 clinical trials. A reduction in NfL may also be a reasonably likely surrogate endpoint for experimental therapeutics administered early in the course of disease.

Occupational lead exposure and survival with amyotrophic lateral sclerosis. Wang TW, Wuu J, Cooley A, Yeh TS, Benatar M, Weisskopf M. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Apr 9;1-8. doi: 10.1080/21678421.2022.2059379. Online ahead of print.

Environmental risk factors are thought to play a role in ALS risk but may also impact the rate of disease progression and survival. Lead, given its known neurotoxicity, is one such exposure. Prior studies that have relied on biomarkers of lead exposure have yielded conflicting results. In this study, researchers evaluated the relationship between occupational lead exposure prior to onset of ALS on the one hand, and disease progression and survival following onset of ALS on the other hand. Lead exposure was determined using a job-exposure matrix based on occupations held prior to onset of ALS. This approach avoids the potential for reverse causation bias that may result from reliance on lead biomarkers after disease onset. The impact on disease progression was quantified through both survival analysis and estimation of the rate of functional decline. Results suggest that lead exposure before onset of ALS is associated with more rapid functional decline and shorter survival following onset of ALS, even after adjusting for other factors known to influence disease progression.

Patient reported impact of symptoms in amyotrophic lateral sclerosis (PRISM-ALS): A national, cross-sectional study. Zizzi C, Seabury J, Rosero S, Alexandrou D, Wagner E, Weinstein JS, Varma A, Dilek N, Heatwole J, Wuu J, Caress J, Bedlack R, Granit V, Statland JM, Mehta P, Benatar M, Heatwole C. EClinicalMedicine. 2022 Dec 13;55:101768. doi: 10.1016/j.eclinm.2022.101768. PMID: 36531982; PMCID: PMC9755057.

Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; First International Pre-Symptomatic ALS Workshop. Brain. 2022 Mar 29;145(1):27-44. doi: 10.1093/brain/awab404. PMID: 34677606; PMCID: PMC8967095.

Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis (ALS). Much is still unknown, however, and advances in other neurodegenerative diseases—including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), spinal muscular atrophy (SMA), and frontotemporal dementia (FTD)—highlight opportunities for discovery in ALS. This article builds on discussions at the First International Pre-Symptomatic ALS Workshop (January 2020, Miami, Florida). Lessons from AD illustrate the importance of conceptualizing neurodegenerative diseases as biological entities. PD and HD, respectively, highlight the value of prodromal clinical markers and the value of tools to predict age of onset. FTD elucidates nuanced differences in pre-symptomatic disease based on genotype, and SMA underscores the value of early therapeutic intervention. The authors discuss a conceptual framework for pre-symptomatic ALS that includes clinically silent and prodromal stages of disease. They also provide recommendations for the study of motor, cognitive, and behavioral manifestations of early ALS; emphasize the critical importance of biomarkers; discuss the challenges of genetic and biomarker counseling as well as a range of ethical, legal, and social issues relevant to pre-symptomatic disease. Last, but not least, they present ideas about the design of early intervention and disease prevention clinical trials. Ultimately, the authors present a road map to early intervention—and perhaps even disease prevention—for all forms of ALS.

Rates of longitudinal change in (18) F-flortaucipir PET vary by brain region, cognitive impairment, and age in atypical Alzheimer's disease. Phillips JS, Nitchie FJ 4th, Da Re F, Olm CA, Cook PA, McMillan CT, Irwin DJ, Gee JC, Dubroff JG, Grossman M, Nasrallah IM; Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2022 Jun;18(6):1235-1247. doi: 10.1002/alz.12456. Epub 2021 Sep 13.

Revealing the Mutational Spectrum in Southern Africans with Amyotrophic Lateral Sclerosis. Nel M, Mahungu AC, Monnakgotla N, Botha GR, Mulder NJ, Wu G, Rampersaud E, van Blitterswijk M, Wuu J, Cooley A, Myers J, Rademakers R, Taylor JP, Benatar M, Heckmann JM. Neurol Genet. 2022 Jan 12;8(1):e654. doi: 10.1212/NXG.0000000000000654. PMID: 35047667; PMCID: PMC8756565.

Amyotrophic Lateral Sclerosis Survival Associates With Neutrophils in a Sex-specific Manner. Murdock BJ, Goutman SA, Boss J, Kim S, Feldman EL. Neurol Neuroimmunol Neuroinflamm. 2021 Feb 2;8(2):e953. doi: 10.1212/NXI.0000000000000953. Print 2021 Mar.

Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations. Lingor P, Koch JC, Statland JM, Hussain S, Hennecke C, Wuu J, Langbein T, Ahmed R, Günther R, Ilse B, Kassubek J, Kollewe K, Kuttler J, Leha A, Lengenfeld T, Meyer T, Neuwirth C, Tostmann R, Benatar M. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug;22(5-6):419-425. doi: 10.1080/21678421.2021.1879866. Epub 2021 Feb 3.

Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD. Ramic M, Andrade NS, Rybin MJ, Esanov R, Wahlestedt C, Benatar M, Zeier Z. Brain Sci. 2021 Nov 20;11(11):1543. doi: 10.3390/brainsci11111543.

Epigenetic small moleculars rescue nucleocytoplasmic transport and DNA damage phenotypes in C9ORF72 ALS/FTD. Melina Ramic, Nadja S Andrade, Matthew J Rybin, Rustam Esanov, Claes Wahlestedt, Michael Benatar, Zane Zeier. Brain Sci. 2021 Nov 20;11(11):1543. doi: 10.3390/brainsci11111543. PMID: 34827542.

FGF23, a novel muscle biomarker detected in the early stages of ALS. Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. Sci Rep. 2021 Jun 8;11(1):12062. doi: 10.1038/s41598-021-91496-6.

Harnessing the power of the electronic health record for ALS research and quality improvement: CReATe CAPTURE-ALS and the ALS Toolkit. Granit V, Grignon AL, Wuu J, Katz J, Walk D, Hussain S, Hernandez J, Jackson C, Caress J, Yosick T, Smider N, Benatar M. Muscle Nerve. 2022 Feb;65(2):154-161. doi: 10.1002/mus.27454. Epub 2021 Nov 16. PMID: 34730240; PMCID: PMC8752483.

Effective use of electronic health record (EHR) data for research purposes has been a long-standing goal of physicians caring for patients with amyotrophic lateral sclerosis (ALS). Several barriers, however, have impeded progress toward this goal, including the limited quality and completeness of clinical documentation, as well as the burden of duplicative entry of clinical data into a research database. To address these barriers, researchers developed the ALS Toolkit, a set of interactive digital forms integrated into the EHR. Used routinely during clinic visits, the ALS Toolkit enables seamless, structured and consistent collection of data elements relevant to ALS patient care, with the expectation that these will also be suitable for research purposes. Since it incorporates AAN quality measures for the care of ALS patients, the ALS Toolkit may also be used to facilitate quality improvement initiatives. CReATe’s Clinical Procedures to Support Research in ALS (CAPTURE-ALS) study utilizes the ALS Toolkit to facilitate multi-center aggregation of data collected at the point of clinical care, empowering research and driving quality improvement. With the goal of collecting data from all patients receiving care through multidisciplinary clinics, CAPTURE-ALS will yield data that reflects the true diversity of populations affected by ALS, rather than the restricted subset of patients currently participating in dedicated research studies.

Humoral response to neurofilaments and dipeptide repeats in ALS progression. Puentes F, Lombardi V, Lu CH, Yildiz O, Fratta P, Isaacs A, Bobeva Y, Wuu J; ALS Biomarker Consortium; CReATe Consortium, Benatar M, Malaspina A. Ann Clin Transl Neurol. 2021 Sep;8(9):1831-1844. doi: 10.1002/acn3.51428. Epub 2021 Jul 27.

Neurofilaments, both light chain (NfL) and phosphorylated neurofilament heavy (pNfH), are structural components of axons. Both NfL and pNfH are known to increase during the pre-symptomatic and early symptomatic phases of disease and then to reach a stable but elevated plateau despite continued progression of disease. Although these proteins, most notably NfL, have emerged as the most promising prognostic and potential pharmacodynamic biomarkers, it remains unclear why neurofilament levels do not change as disease progresses. The current study focused on the immune response to neurofilaments (and dipeptide repeat proteins in patients with the C9orf72 genetic form of ALS), quantifying levels of antibodies and immune complexes that represent the humeral response to the release of these proteins. The investigators observed a trend towards increasing concentrations of NfL antibodies and immune complexes over the course of longitudinal follow among patients with faster progressing disease, raising the possibility that the immune response is partially responsible for clearing NfL and stabilizing plasma levels of this protein despite increased production as neurodegeneration progresses.

Long-read targeted sequencing ucnovers clinicopathological associations for Cr0rf72-linked diseases. DeJesus-Hernandez M, Aleff RA, Jackson JL, Finch NA, Baker MC, Gendron TF, Murray ME, McLaughlin IJ, Harting JR, Graff-Radford NR, Oskarsson B, Knopman DS, Josephs KA, Boeve BF, Petersen RC, Fryer JD, Petrucelli L, Dickson DW, Rademakers R, Ebbert MTW, Wieben ED, van Blitterswijk M.. Brain. 2021 May 7;144(4):1082-1088. doi: 10.1093/brain/awab006. PMID: 33889947.

Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis. Placek K, Benatar M, Wuu J, Rampersaud E, Hennessy L, Van Deerlin VM, Grossman M, Irwin DJ, Elman L, McCluskey L, Quinn C, Granit V, Statland JM, Burns TM, Ravits J, Swenson A, Katz J, Pioro EP, Jackson C, Caress J, So Y, Maiser S, Walk D, Lee EB, Trojanowski JQ, Cook P, Gee J, Sha J, Naj AC, Rademakers R; CReATe Consortium, Chen W, Wu G, Paul Taylor J, McMillan CT. EMBO Mol Med. 2020 Dec 3;e12595. PMID: 3327098.

NK cells associate with ALS in a sex- and age-dependent manner. Murdock BJ, Famie JP, Piecuch CE, Raue KD, Mendelson FE, Pieroni CH, Iniguez SD, Zhao L, Goutman SA, Feldman EL. JCI Insight. 2021 Jun 8;6(11):e147129. doi: 10.1172/jci.insight.147129.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia. Kessler C, Serna-Higuita LM, Rattay TW, Maetzler W, Wurster I, Hayer S, Wilke C, Hengel H, Reichbauer J, Armbruster M, Schöls L, Martus P, Schüle R. Ann Clin Transl Neurol. 2021 May;8(5):1122-1131. doi: 10.1002/acn3.51358. Epub 2021 Apr 5.

Repeats expansions in ATXN2, NOP56, NIPA1 and ATXN1 are not associated with ALS in Africans. Nel M, Mavundla T, Gultig K, Botha G, Mulder N, Benatar M, Wuu J, Cooley A, Myers J, Rampersaud E, Wu G, Heckmann JM. IBRO Neurosci Rep. 2021 Feb 10;10:130-135. doi: 10.1016/j.ibneur.2021.02.002. eCollection 2021 Jun.

Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis. Shepheard SR, Karnaros V, Benyamin B, Schultz DW, Dubowsky M, Wuu J, Chataway T, Malaspina A, Benatar M, Rogers ML. Eur J Neurol. 2021 Dec 29. doi: 10.1111/ene.15237. Epub ahead of print. PMID: 34967083.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that leads to progressive muscle weakness. There are currently no meaningfully effective treatments for ALS, which is invariably fatal. Biomarkers that are suitably fit-for-purpose have great potential to enhance therapy development efforts. A research team led by Dr. Mary Louise-Rogers at Flinders University in Australia has found that urinary neopterin, a marker of an underlying pro-inflammatory state, is elevated in ALS compared to age-matched controls, and progressively increases as the disease advances. In addition to its potential utility as a biomarker of disease progression, neopterin might also have potential as a predictive biomarker, identifying a subset of patients who may stand to benefit from therapeutics that target inflammatory pathways.

Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD. Andrade N, Ramic M, Esanov R, et al. Mol Neurodegener. 2020; 15: 13. PMCID:PMC7041170, PMID: 32093728.

Disentangling Heterogeneity in Alzheimer's Disease and Related Dementias Using Data-Driven Methods. Habes M, Grothe MJ, Tunc B, McMillan C, Wolk DA, Davatzikos C. Biol Psychiatry. 2020 Jul 1;88(1):70-82. doi: 10.1016/j.biopsych.2020.01.016. Epub 2020 Jan 31.

Metabolite Profiling Reveals Predictive Biomarkers and the Absence of β-Methyl Amino-l-alanine in Plasma from Individuals Diagnosed with Amyotrophic Lateral Sclerosis. Bereman MS, Kirkwood KI, Sabaretnam T, Furlong S, Rowe DB, Guillemin GJ, Mellinger AL, Muddiman DC. J Proteome Res. 2020 Aug 7;19(8):3276-328. PMID: 32418425.

Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice. Figueroa-Romero C,1, Guo K,2, Murdock BJ, et al. Dis Model Mech. 2020 Feb 1; 13(2). PMCID: PMC6906635, PMID: 31597644.

The potential of neurofilaments analysis using dry-blood and plasma spots. Lombardi V, Carassiti D, Giovannoni G, Lu CH, Adiutori R, Malaspina A. Sci Rep. 2020 Jan 9;10(1):97. PMID: 31919375, PMCID: PMC6952412.

Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, Swenson A, Ravits J, Jackson C, Burns TM, Trivedi J, Pioro EP, Caress J, Katz J, McCauley JL, Rademakers R, Malaspina A, Ostrow LW, Wuu J; CReATe Consortium. Neurology. 2020 Jul 7;95(1):e59-e69. PMID: 32385188, PMCID: PMC7371380.

Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study. Aladesuyi Arogundade O, Stauffer JE, Saberi S, Diaz-Garcia S, Malik S, Basilim H, Rodriguez MJ, Ohkubo T, Ravits J. Acta Neuropathol. 2019. PMID: 30666413.

Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Farhan SMK, Howrigan DP, Abbott LE, Klim JR, Topp SD, Byrnes AE, Churchhouse C, Phatnani H, Smith BN, Rampersaud E, Wu G, Wuu J, Shatunov A, Iacoangeli A, Al Khleifat A, Mordes DA, Ghosh S; ALSGENS Consortium; FALS Consortium; Project MinE Consortium; CReATe Consortium, Eggan K, Rademakers R, McCauley JL, Schüle R, Züchner S, Benatar M, Taylor JP, Nalls M, Gotkine M, Shaw PJ, Morrison KE, Al-Chalabi A, Traynor B, Shaw CE, Goldstein DB, Harms MB, Daly MJ, Neale BM. Nat Neurosci. 2019 Dec; 22(12): 1966–1974. PMCID: PMC6919277, PMID: 31768050.

Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants. Edmonson MN, Patel AN, Hedges DJ, Wang Z, Rampersaud E, Kesserwan CA, Zhou X, Liu Y, Newman S, Rusch MC, McLeod CL, Wilkinson MR, Rice SV, Soussi T, Taylor JP, Benatar M, Becksfort JB, Nichols KE, Robison LL, Downing JR, Zhang J.. Genome Res. 2019 Sep;29(9):1555-1565. doi: 10.1101/gr.250357.119. Epub 2019 Aug 22. PMID: 31439692.

UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis. Placek K, Baer GM, Elman L, McCluskey L, Hennessy L, Ferraro PM, Lee EB, Lee VMY, Trojanowski JQ, Van Deerlin VM, Grossman M, Irwin DJ, McMillan CT. Neurobiol Aging. 2019; 73:190-199. PMID:30368160, PMCID: PMC6251755.

G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo. Simone R, Balendra R, Moens TG, et al. EMBO Mol Med. 2018;10(1):22-31. PMID: 29113975, PMCID: PMC5760849.

GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Eidhof I, Baets J, Kamsteeg EJ, Deconinck T, van Ninhuijs L, Martin JJ, Schüle R, Züchner S, De Jonghe P, Schenck A, van de Warrenburg BP. Brain. 2018 Sep 1;141(9):2592-2604. doi: 10.1093/brain/awy198.

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, et al. Neuron. 2018;97(6):1268-1283.e1266. PMID: 29566793, PMCID: PMC5867896.

Identification of compound heterozygous variants in OPTN in an ALS-FTD patient from the CReATe consortium: a case report. Pottier C, Rampersaud E, Baker M, Wu G, Wuu J, McCauley JL, Zuchner S, Schule R, Bermudez C, Hussain S, Cooley A, Wallace M, Zhang J, Taylor JP, Benatar M, Rademakers R. Amyotrophic lateral sclerosis & frontotemporal degeneration. 2018:1-3. PMID: 29558868.

Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brožková DŠ, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Am J Hum Genet. 2018;102(3):505-514. PMID: 29499166, PMCID: PMC5985288.

Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS/FTD. Moens TG, Mizielinska S, Niccoli T, et al. Acta Neuropathol. 2018;135(3):445-457. PMID:29380049.

Serum neurofilament light chain is increased in hereditary spastic paraplegias. Wilke C, Rattay TW, Hengel H, Zimmermann M, Brockmann K, Schöls L, Kuhle J, Schüle R, Synofzik M. Annals of clinical and translational neurology. 2018;5(7):876-882. PMID:30009206, PMCID: PMC6043776.

Using automated electronic medical record data extraction to model ALS survival and progression. Karanevich AG, Weisbrod LJ, Jawdat O, Barohn RJ, Gajewski BJ, He J, Statland JM. BMC Neurol. 2018;18(1):205. PMID:30547800, PMCID: PMC6295028.

A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD. Esanov R, Cabrera GT, Andrade NS, Gendron TF, Brown RH Jr, Benatar M, Wahlestedt C, Mueller C, Zeier Z. Mol Neurodegener. 2017;12(1):46. PMID: 28606110, PMCID: PMC5468954.

Abnormal expression of homeobox genes and transthyretin in C9ORF72 expansion carriers. Finch NA, Wang X, Baker MC, Heckman MG, Gendron TF, Bieniek KF, Wuu J, DeJesus-Hernandez M, Brown PH, Chew J, Jansen-West KR, Daughrity LM, Nicholson AM, Murray ME, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Petrucelli L, Boeve BF, Graff-Radford NR, Asmann YW, Dickson DW, Benatar M, Bowser R, Boylan KB, Rademakers R, van Blitterswijk M. Neurology Genetics. 2017;3(4):e161. PMID: 28660252, PMCID. PMC5479438.

Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Strong MJ, Abrahams S, Goldstein LH, Woolley S, Mclaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, HortobáGyi T, Rosenfeld J, Silani V, Ince PG, Turner MR. Amyotrophic lateral sclerosis & frontotemporal degeneration. 2017;18(3-4):153-174. PMID: 28054827.

Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression. Murdock BJ, Zhou T, Kashlan SR, Little RJ, Goutman SA, Feldman EL. JAMA neurology. 2017. PMID: 28973548, PMCID: PMC5822195.

Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Jacquier A, Delorme C, Belotti E, Juntas-Morales R, Solé G, Dubourg O, Giroux M, Maurage CA, Castellani V, Rebelo A, Abrams A, Züchner S, Stojkovic T, Schaeffer L, Latour P. Acta neuropathologica communications. 2017;5(1):55. PMID: 28709447, PMCID: PMC5513089.

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R. Brain. 2017;140(12):3112-3127. PMID:29126212, PMCID: PMC5841036.

In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers. DeJesus-Hernandez M, Finch NA, Wang X, Gendron TF, Bieniek KF, Heckman MG, Vasilevich A, Murray ME, Rousseau L, Weesner R, Lucido A, Parsons M, Chew J, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Graff-Radford NR, de Boer J, Asmann YW, Petrucelli L, Boylan KB, Dickson DW, van Blitterswijk M, Rademakers R. Acta Neuropathol. 2017;134(2):255-269. PMID: 28508101, PMCID: PMC5508036.

Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF; C9ORF72 Neurofilament Study Group, Daughrity LM, Heckman MG, Diehl NN, Wuu J, Miller TM, Pastor P, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Benatar M, Silani V, Glass JD, Floeter MK, Jeromin A, Boylan KB, Petrucelli L. Ann Neurol. 2017;82(1):139-146. PMID: 28628244, PMCID: PMC5676468.

Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O'Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L. Sci Transl Med. 2017;9(383). PMID: 28356511, PMCID: PMC5576451.

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients. Prudencio M, Gonzales PK, Cook CN, Gendron TF, Daughrity LM, Song Y, Ebbert MTW, van Blitterswijk M, Zhang YJ, Jansen-West K, Baker MC, DeTure M, Rademakers R, Boylan KB, Dickson DW, Petrucelli L, Link CD. Hum Mol Genet. 2017;26(17):3421-3431. PMID: 28637276.

Research Toolkit: Capturing clinical data to advance ALS research. Michael Benatar, Jonathan Katz, David Walk CReATe Consortium ALS Association Muscular Dystrophy Association (MDA). Capturing clinical data to advance ALS research. https://galaxy.epic.com/Redirect.aspx?DocumentID=3701881&Version=Epic 2017, EpicCare Ambulatory, 2017.

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, Annu K, Baker M, Perkerson RB, Kurti A, Matchett BJ, Mittag T, Temirov J, Hsiung GR, Krieger C, Murray ME, Kato M, Fryer JD, Petrucelli L, Zinman L, Weintraub S, Mesulam M, Keith J, Zivkovic SA, Hirsch-Reinshagen V, Roos RP, Züchner S, Graff-Radford NR, Petersen RC, Caselli RJ, Wszolek ZK, Finger E, Lippa C, Lacomis D, Stewart H, Dickson DW, Kim HJ, Rogaeva E, Bigio E, Boylan KB, Taylor JP, Rademakers R. Neuron. 2017;95(4):808-816.e809. PMID: 28817800, PMCID: PMC5576574.

Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Shepheard SR, Wuu J, Cardoso M, Wiklendt L, Dinning PG, Chataway T, Schultz D, Benatar M, Rogers ML. Neurology. 2017;88(12):1137-1143. PMID: 28228570, PMCID: PMC5373786.

ALS biomarkers for therapy development: State of the field and future directions. Benatar M, Boylan K, Jeromin A, Rutkove SB, Berry J, Atassi N, Bruijn L. Muscle Nerve. Feb 2016;53(2):169-182. PMID: 26574709, PMCID: PMC4718795.

C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD. Liu Y, Pattamatta A, Zu T, et al. Neuron. 2016;90(3):521-534. PMID: 27112499.

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells. Esanov R, Belle KC, van Blitterswijk M, Belzil VV, Rademakers R, Dickson DW, Petrucelli L, Boylan KB, Dykxhoorn DM, Wuu J, Benatar M, Wahlestedt C, Zeier Z. Exp Neurol. Mar 2016;277:171-177. PMID: 26746986, PMCID: PMC4761318.

Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Rebelo AP, Abrams AJ, Cottenie E, Horga A, Gonzalez M, Bis DM, Sanchez-Mejias A, Pinto M, Buglo E, Markel K, Prince J, Laura M, Houlden H, Blake J, Woodward C, Sweeney MG, Holton JL, Hanna M, Dallman JE, Auer-Grumbach M, Reilly MM, Zuchner S. Am J Hum Genet. 2016; 98(4):597-614. PMID: 27040688, PMCID: PMC4833435.

Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis. Murdock BJ, Bender DE, Kashlan SR, et al. Neurology(R) neuroimmunology & neuroinflammation. 2016;3(4):e242. PMID: 27308304, PMCID: PMC4897983.

Presymptomatic ALS genetic counseling and testing: Experience and recommendations. Benatar M, Stanislaw C, Reyes E, Hussain S, Cooley A, Fernandez MC, Dauphin DD, Michon SC, Andersen PM, Wuu J.. Neurology. 2016 Jun 14;86(24):2295-302. doi: 10.1212/WNL.0000000000002773. Epub 2016 May 18.

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers. Gendron TF, van Blitterswijk M, Bieniek KF, Daughrity LM, Jiang J, Rush BK, Pedraza O, Lucas JA, Murray ME, Desaro P, Robertson A, Overstreet K, Thomas CS, Crook JE, Castanedes-Casey M, Rousseau L, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Graff-Radford NR, Rademakers R, Lagier-Tourenne C, Edbauer D, Cleveland DW, Dickson DW, Petrucelli L, Boylan KB. Acta Neuropathol. Oct 2015;130(4):559-573. PMID: 26350237, PMCID: PMC4575385.

Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis. Turner MR, Benatar M. Muscle Nerve. Jan 2015;51(1):14-18. PMID: 25288265, PMCID: PMC4270289.

Neurodegenerative disease: C9orf72 repeats compromise nucleocytoplasmic transport. van Blitterswijk M, Rademakers R. Nature reviews. Neurology. Dec 2015;11(12):670-672. PMID: 26526532.

Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72. van Blitterswijk M, Gendron TF, Baker MC, DeJesus-Hernandez M, Finch NA, Brown PH, Daughrity LM, Murray ME, Heckman MG, Jiang J, Lagier-Tourenne C, Edbauer D, Cleveland DW, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Petrucelli L, Boeve BF, Graff-Radford NR, Boylan KB, Dickson DW, Rademakers R. Acta Neuropathol. Oct 5 2015. PMID: 26437865, PMCID: PMC4655160.

Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Brain. Feb 2015;138(Pt 2):293-310. PMID: 25497877, PMCID: PMC4306822.

Maternal and Perinatal Outcomes Associated With the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. Seasely AR, Blanchard CT, Arora N, Battarbee AN, Casey BM, Dionne-Odom J, Leal SM Jr, Moates DB, Sinkey RG, Szychowski JM, Tita AT, Subramaniam A; CWRH's COVID-19 Working Group;. Obstet Gynecol. 2022 Aug 1;140(2):262-265. doi: 10.1097/AOG.0000000000004849. Epub 2022 May 18. PMID: 35852277.

Maternal and Perinatal Outcomes Associated With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) Variant. Seasely AR, Blanchard CT, Arora N, Battarbee AN, Casey BM, Dionne-Odom J, Leal SM Jr, Moates DB, Sinkey RG, Szychowski JM, Tita AT, Subramaniam A; CWRH COVID-19 Working Group. Obstet Gynecol. 2021 Dec 1;138(6):842-844. doi: 10.1097/AOG.0000000000004607. PMID: 34592747.

A MULTICENTER LONG-TERM COHORT STUDY OF EOSINOPHILIC ESOPHAGITIS VARIANTS AND THEIR PROGRESSION TO EOE OVER TIME. Greuter T, Straumann A, Fernandez-Marrero Y, Germic N, Hosseini A, Chanwangpong A, Yousefi S, Simon D, Collins MH, Bussmann C, Chehade M, Dellon ES, Furuta GT, Gonsalves N, Hirano I, Moawad FJ, Biedermann L, Safroneeva E, Schoepfer AM, Simon HU. Clin Transl Gastroenterol. 2024 Feb 6. doi: 10.14309/ctg.0000000000000664. Epub ahead of print. PMID: 38318864.

Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. Recently, conditions with symptoms of esophageal dysfunction resembling EoE—but without high amounts of eosinophils in the esophagus—have been characterized as EoE variants. However, not much is known about the progression and severity of these variants.

In this study, researchers investigated the progression of EoE variants to EoE over time. The team assessed clinical, immuno-histological, and molecular features of 54 patients with EoE variants from six EoE centers. Findings were compared with features of EoE patients and healthy controls.

Results suggest a disease spectrum, based on transition from EoE variants to EoE. Authors note that genes associated with the progression to EoE may represent potential therapeutic targets early in the course of disease. 

Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial. Kliewer KL, Murray-Petzold C, Collins MH, Abonia JP, Bolton SM, DiTommaso LA, Martin LJ, Zhang X, Mukkada VA, Putnam PE, Kellner ES, Devonshire AL, Schwartz JT, Kunnathur VA, Rosenberg CE, Lyles JL, Shoda T, Klion AD, Rothenberg ME. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):803-815. doi: 10.1016/S2468-1253(23)00145-0. Epub 2023 Jun 16.

Biologics in eosinophilic gastrointestinal diseases. Dellon ES, Spergel JM. Ann Allergy Asthma Immunol. 2023 Jan;130(1):21-27. doi: 10.1016/j.anai.2022.06.015. Epub 2022 Jun 20.

Breaking down the complex pathophysiology of eosinophilic esophagitis. Underwood B, Troutman TD, Schwartz JT. Ann Allergy Asthma Immunol. 2023 Jan;130(1):28-39. doi: 10.1016/j.anai.2022.10.026. Epub 2022 Nov 6.

Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting. Chehade M, Wright BL, Atkins D, Aceves SS, Ackerman SJ, Assa'ad AH, Bauer M, Collins MH, Commins SP, Davis CM, Dellon ES, Doerfler B, Gleich GJ, Gupta SK, Hill DA, Jensen ET, Katzka D, Kliewer K, Kodroff E, Kottyan LC, Kyle S, Muir AB, Pesek RD, Peterson K, Shreffler WG, Spergel JM, Strobel MJ, Wechsler J, Zimmermann N, Furuta GT, Rothenberg ME. J Allergy Clin Immunol. 2023 Sep 1:S0091-6749(23)01103-X. doi: 10.1016/j.jaci.2023.08.021. Online ahead of print.

Eosinophilic gastrointestinal disorders (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. 

In February 2022, the American Academy of Allergy, Asthma, and Immunology hosted their annual meeting to discuss innovations in research. During the meeting, CEGIR and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium focused on breakthrough discoveries in EGIDs.

The symposium featured a review of recent discoveries in the basic biology, pathogenesis, and clinical features of EGIDs. Topics included diagnostic and management approaches, as well as clinical trials of emerging therapies.

Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Doyle AD, Masuda MY, Pyon GC, Luo H, Putikova A, LeSuer WE, Flashner S, Rank MA, Nakagawa H, Kita H, Wright BL. Allergy. 2023 Jan;78(1):192-201. doi: 10.1111/all.15457. Epub 2022 Aug 8.

Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis. Chang JW, Kliewer K, Haller E, Lynett A, Doerfler B, Katzka DA, Peterson KA, Dellon ES, Gonsalves N; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1690-1698. doi: 10.1016/j.cgh.2023.03.006. Epub 2023 Mar 16.

Dysphagia Days as an Assessment of Clinical Treatment Outcome in Eosinophilic Esophagitis. Hirano I, Rothenberg ME, Zhang S, de Oliveira C, Charriez CM, Coyne KS, Bacci ED, Dellon ES. Am J Gastroenterol. 2023 Apr 1;118(4):744-747. doi: 10.14309/ajg.0000000000002094. Epub 2022 Dec 20.

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Rothenberg ME, Dellon ES, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Sun X, Hamilton JD, Mortensen E, Laws E, Maloney J, Mannent LP, McCann E, Liu X, Glotfelty L, Shabbir A. Lancet Gastroenterol Hepatol. 2023 Aug 31:S2468-1253(23)00204-2. doi: 10.1016/S2468-1253(23)00204-2. Online ahead of print.

Enhancing diversity, equity, inclusion, and accessibility in eosinophilic gastrointestinal disease research: the consortium for eosinophilic gastrointestinal disease researchers' journey. Chehade M, Furuta G, Klion A, Abonia JP, Aceves S, Bose P, Collins MH, Davis C, Dellon ES, Eickel G, Falk G, Gupta S, Hiremath G, Howard A, Jensen ET, Kesh S, Khoury P, Kocher K, Kodroff E, Kyle S, Mak N, McCoy D, Mehta P, Menard-Katcher P, Mukkada V, Paliana A, Rothenberg M, Sable K, Schmitt C, Scott M, Spergel J, Strobel MJ, Wechsler JB, Yang GY, Zicarelli A, Muir AB, Wright BL, Bailey DD. Ther Adv Rare Dis. 2023 Aug 14;4:26330040231180895. doi: 10.1177/26330040231180895. PMID: 37588777; PMCID: PMC10426297

Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic immune system disorders in which inflammation causes difficulties in daily life and the buildup of a type of white blood cell (eosinophils) in the gastrointestinal tract, which can lead to tissue damage and dysfunction.

To address systemic bias in patient care and research in EGIDs, the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee. The CEGIR diversity committee has defined its purpose through mission and vision statements. The committee has also developed structured educational and research initiatives to enhance diversity, equity, inclusivity, and accessibility (DEIA) in all CEGIR activities.

In this review article, researchers share the process of forming the diversity committee, highlighting milestones achieved and summarizing future directions. Authors hope that this report will serve as a guide and an inspiration for other researchers to enhance DEIA in their fields.

Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023. Salvador Nunes VS, Straumann A, Salvador Nunes L, Schoepfer AM, Greuter T. Int Arch Allergy Immunol. 2023;184(5):411-420. doi: 10.1159/000529910. Epub 2023 Mar 27.

Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis. Hiremath G, Sun L, Collins MH, Bonis PA, Arva NC, Capocelli KE, Chehade M, Davis CM, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Khoury P, Mukkada VA, Martin LJ, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME, Koyama T, Dellon ES. Clin Gastroenterol Hepatol. 2023 Mar 24:S1542-3565(23)00222-7. doi: 10.1016/j.cgh.2023.03.014. Online ahead of print.

Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. The nature of the involvement of esophageal tissue has been unclear.

In this study, the investigators estimated the intrabiopsy site agreements of an established EoE histologic scoring system (EoEHSS) in the esophageal epithelial and lamina propria and examined if the disease activity status influenced the intrabiopsy site agreement. Comparisons were made between proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites.

Results show that except for the extent of dilated intercellular spaces in inactive EoE, epithelial features and lamina propria were unevenly affected across esophageal biopsy sites, regardless of disease status. Authors note that these findings enhance our understanding of the effects of EoE on esophageal tissue pathology.

Examining Disparities in Pediatric Eosinophilic Esophagitis. Mehta P, Pan Z, Zhou W, Burger C, Menard-Katcher C, Bailey DD, Furuta GT. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2855-2859. doi: 10.1016/j.jaip.2023.06.011. Epub 2023 Jun 14.

Food-Specific IgG4 Is Elevated Throughout the Upper Gastrointestinal Tract in Eosinophilic Esophagitis. Masuda MY, LeSuer WE, Horsley-Silva JL, Putikova A, Buras MR, Gibson JB, Pyon GC, Simmons TD, Doyle AD, Wright BL. Dig Dis Sci. 2023 Jun;68(6):2406-2413. doi: 10.1007/s10620-023-07924-2. Epub 2023 Mar 27.

Genome-wide admixture and association analysis identifies African ancestry-specific risk loci of eosinophilic esophagitis in African Americans. Gautam Y, Caldwell J, Kottyan L, Chehade M, Dellon ES, Rothenberg ME, Mersha TB; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) investigators. J Allergy Clin Immunol. 2023 May;151(5):1337-1350. doi: 10.1016/j.jaci.2022.09.040. Epub 2022 Nov 15.

Local type 2 immunity in eosinophilic gastritis. Ben-Baruch Morgenstern N, Shoda T, Rochman Y, Caldwell JM, Collins MH, Mukkada V, Putnam PE, Bolton SM, Felton JM, Rochman M, Murray-Petzold C, Kliewer KL, Rothenberg ME. J Allergy Clin Immunol. 2023 Jul;152(1):136-144. doi: 10.1016/j.jaci.2023.01.021. Epub 2023 Feb 7.

Molecular analysis of duodenal eosinophilia. Shoda T, Rochman M, Collins MH, Caldwell JM, Mack LE, Osswald GA, Mukkada VA, Putnam PE, Rothenberg ME. J Allergy Clin Immunol. 2023 Apr;151(4):1027-1039. doi: 10.1016/j.jaci.2022.12.814. Epub 2022 Dec 30.

Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis. Furuta GT, Fillon SA, Williamson KM, Robertson CE, Stevens MJ, Aceves SS, Arva NC, Chehade M, Collins MH, Davis CM, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Leung J, Martin LJ, Menard-Katcher P, Mukkada VA, Peterson K, Spergel JM, Wechsler JB, Yang GY, Rothenberg ME, Harris JK. J Pediatr Gastroenterol Nutr. 2023 Mar 1;76(3):347-354. doi: 10.1097/MPG.0000000000003685. Epub 2022 Dec 16. PMID: 36525669.

Eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) are disorders in which eosinophils (white blood cells) of the immune system build up as a reaction to foods or allergens, causing tissue damage. This immune response occurs in the esophagus in EoE and in the stomach in EoG. To better understand the association of gut microbiota (microorganisms in the digestive tract) with EoE and EoG, multicenter studies with large patient cohorts are needed.

In this study, researchers identified the mucosal microbiota associated with EoE and EoG in a geographically diverse cohort of patients. The team collected and analyzed clinical data, mucosal biopsies, and stool of pediatric and adult individuals with eosinophilic gastrointestinal disease (EGID) from 10 clinical sites within the Consortium of Eosinophilic Gastrointestinal Disease Researchers.

Not surprisingly, microbiome samples collected in the esophagus and stomach were not similar to those collected in the stool, thus emphasizing the importance of site-specific capture of data. Taxa associated with EGIDs varied highly among individuals. Authors note that further research is needed to determine if therapeutic interventions contribute to these differences.

One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial. Kliewer KL, Gonsalves N, Dellon ES, Katzka DA, Abonia JP, Aceves SS, Arva NC, Besse JA, Bonis PA, Caldwell JM, Capocelli KE, Chehade M, Cianferoni A, Collins MH, Falk GW, Gupta SK, Hirano I, Krischer JP, Leung J, Martin LJ, Menard-Katcher P, Mukkada VA, Peterson KA, Shoda T, Rudman Spergel AK, Spergel JM, Yang GY, Zhang X, Furuta GT, Rothenberg ME. Lancet Gastroenterol Hepatol. 2023 May;8(5):408-421. doi: 10.1016/S2468-1253(23)00012-2. Epub 2023 Feb 28.

Prospective study of an amino acid-based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial. Gonsalves N, Doerfler B, Zalewski A, Yang GY, Martin LJ, Zhang X, Shoda T, Brusilovsky M, Aceves S, Thompson K, Rudman Spergel AK, Furuta G, Rothenberg ME, Hirano I. J Allergy Clin Immunol. 2023 Sep;152(3):676-688. doi: 10.1016/j.jaci.2023.05.024. Epub 2023 Jul 18.

Quality Indicators for the Diagnosis and Management of Eosinophilic Esophagitis. Leiman DA, Kamal AN, Otaki F, Bredenoord AJ, Dellon ES, Falk GW, Fernandez-Becker NQ, Gonsalves N, Hirano I, Katzka DA, Peterson K, Yadlapati R, Kathpalia P. Am J Gastroenterol. 2023 Jun 1;118(6):1091-1095. doi: 10.14309/ajg.0000000000002138. Epub 2022 Dec 23.

Recent Advances in the Treatment of Eosinophilic Esophagitis. Uchida AM, Burk CM, Rothenberg ME, Furuta GT, Spergel JM. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2654-2663. doi: 10.1016/j.jaip.2023.06.035. Epub 2023 Jun 28.

The Cellie Coping Kit for children with Eosinophilic Esophagitis: Feasibility, acceptability, and preliminary outcomes. Benitez AJ, McGar A, Kohser K, Gibbons T, Muir A, Mascarenhas M, Rossi C, Dogias F, Golden A, Kassam-Adams N, Marsac ML. J Child Health Care. 2023 Sep;27(3):374-385. doi: 10.1177/13674935211064126. Epub 2022 Jan 3.

The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders. Sindher SB, Barshow S, Tirumalasetty J, Arasi S, Atkins D, Bauer M, Bégin P, Collins MH, Deschildre A, Doyle AD, Fiocchi A, Furuta GT, Garcia-Lloret M, Mennini M, Rothenberg ME, Spergel JM, Wang J, Wood RA, Wright BL, Zuberbier T, Chin AR, Long A, Nadeau KC, Chinthrajah RS. J Allergy Clin Immunol. 2023 Mar;151(3):595-606. doi: 10.1016/j.jaci.2023.01.007. PMID: 36872039; PMCID: PMC9993424.

Eosinophilic gastrointestinal disorders (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. EGIDs and food allergy (FA) share similar inflammatory mechanisms. Because of this, many of the same biologics (medications developed from biological sources) are being investigated to target these mechanisms in both EGIDs and FA.

In this review article, a team of researchers led by CEGIR scholars discuss the enormous potential of biologics for the treatment of EGIDs and FA in pediatric patients. Discussion includes past and current research into the use of biologics in FA and EGIDs, as well as their potential role in improving treatment options in the future. Authors also note the need for wider availability of biologics for clinical use.

2021 year in review: Spotlight on eosinophils. Dunn JLM, Rothenberg ME. J Allergy Clin Immunol. 2022 Feb;149(2):517-524. doi: 10.1016/j.jaci.2021.11.012. Epub 2021 Nov 25.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. Gastroenterology. 2022 Jul;163(1):59-76. doi: 10.1053/j.gastro.2022.03.025. Epub 2022 May 20. PMID: 35606197; PMCID: PMC9233087.

For patients with eosinophilic esophagitis (EoE), an allergic inflammatory disease that damages the esophagus, therapeutic options and management are dictated by disease severity. However, the process for determining severity varies among practitioners. Reducing this variability could help improve clinicians’ ability to monitor EoE in an office setting. In this study, researchers aimed to create an international consensus severity scoring index for EoE. First, a group of adult and pediatric EoE researchers and clinicians—as well as non-EoE allergy immunology and gastroenterology experts—reviewed existing literature on EoE in the context of progression and severity. Next, a steering committee reached consensus on important features of severity. These features were then distilled to categorize patients with EoE as having inactive, mild, moderate, or severe disease. This new simplified scoring system, called the Index of Severity for Eosinophilic Esophagitis (I-SEE), can be completed at routine clinic visits. The system can help guide practitioners in EoE management by standardizing features of disease severity beyond eosinophil counts. To increase its utilization and functionality, authors note that I-SEE should be validated and refined using data from future clinical trials and routine clinical practice.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. J Allergy Clin Immunol. 2022 Jul;150(1):33-47. doi: 10.1016/j.jaci.2022.03.015. Epub 2022 May 20.

A Deep Multi-Label Segmentation Network For Eosinophilic Esophagitis Whole Slide Biopsy Diagnostics. Daniel N, Larey A, Aknin E, Osswald GA, Caldwell JM, Rochman M, Collins MH, Yang GY, Arva NC, Capocelli KE, Rothenberg ME, Savir Y. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:3211-3217. doi: 10.1109/EMBC48229.2022.9871086.

A survey examining the impact of COVID-19 on food protein-induced enterocolitis syndrome. Trogen B, Jin H, Cianferoni A, Chehade M, Schultz F, Chavez A, Warren C, Nowak-Wegrzyn AH. J Allergy Clin Immunol Pract. 2022 Jan;10(1):312-314.e3. doi: 10.1016/j.jaip.2021.10.053. Epub 2021 Nov 2.

CD73(+) Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis. Hara T, Kasagi Y, Wang J, Sasaki M, Aaron B, Karami A, Shimonosono M, Shimonosono R, Maekawa H, Dolinsky L, Wilkins B, Klein J, Wei J, Nunes K, Lynch K, Spergel JM, Hamilton KE, Ruffner MA, Karakasheva TA, Whelan KA, Nakagawa H, Muir AB. Cell Mol Gastroenterol Hepatol. 2022;13(5):1449-1467. doi: 10.1016/j.jcmgh.2022.01.018. Epub 2022 Jan 30.

Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study. Greuter T, Straumann A, Fernandez-Marrero Y, Germic N, Hosseini A, Yousefi S, Simon D, Collins MH, Bussmann C, Chehade M, Dellon ES, Furuta GT, Gonsalves N, Hirano I, Moawad FJ, Biedermann L, Safroneeva E, Schoepfer AM, Simon HU. Allergy. 2022 Aug;77(8):2520-2533. doi: 10.1111/all.15233. Epub 2022 Feb 17. PMID: 35094416.

Eosinophilic esophagitis (EoE) is an allergic condition characterized by inflammation in the esophagus that causes a range of symptoms. Patients can have symptoms of esophageal dysfunction without meeting the classical diagnostic criteria. To characterize and classify the range of variants, an international team of researchers studied 69 patients with EoE variants. They identified and described three histological subtypes. Study authors concluded that EoE variants appear to be part of a disease spectrum, with classical EoE as the most common and apparent phenotype.

Close follow-up is associated with fewer stricture formation and results in earlier detection of histological relapse in the long-term management of eosinophilic esophagitis. Bon L, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Vavricka SR, Schoepfer AM, McCright-Gill T, Simon HU, Straumann A, Chehade M, Greuter T. United European Gastroenterol J. 2022 Apr;10(3):308-318. doi: 10.1002/ueg2.12216. Epub 2022 Apr 5. PMID: 35384368.

Eosinophilic esophagitis (EoE) is characterized by immune cells called eosinophils building up in the esophagus, which may cause polyps, tissue break down, inflammation, and ulcers. The follow-up schedule for maintenance treatment of EoE varies, possibly due to a lack of a recommended schedule. In this study, researchers analyzed "close follow-up" (less than 18 months between maintenance visits) and "non-close follow-up" (greater than or equal to 18 months between maintenance visits) for steroid treatment of EoE. They found that close follow-up was associated with less stricture formation (abnormal narrowing) and earlier detection of EoE relapse by histology. Authors note that regular assessment of EoE disease activity (every 12-18 months) may be beneficial in detecting relapsing disease as early as possible, therefore potentially minimizing the risk for EoE complications.

Defining the Patchy Landscape of Esophageal Eosinophilia in Children With Eosinophilic Esophagitis. Wechsler JB, Bolton SM, Gray E, Kim KY, Kagalwalla AF. Clin Gastroenterol Hepatol. 2022 Sep;20(9):1971-1976.e2. doi: 10.1016/j.cgh.2021.12.023. Epub 2021 Dec 23.

Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.

Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis. Hiremath G, Sun L, Correa H, Acra S, Collins MH, Bonis P, Arva NC, Capocelli KE, Falk GW, King E, Gonsalves N, Gupta SK, Hirano I, Mukkada VA, Martin LJ, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME, Koyama T, Dellon ES. Am J Gastroenterol. 2022 Feb 1;117(2):272-279. doi: 10.14309/ajg.0000000000001587.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS). COREOS Collaborators:, Ma C, Schoepfer AM, Dellon ES, Bredenoord AJ, Chehade M, Collins MH, Feagan BG, Furuta GT, Gupta SK, Hirano I, Jairath V, Katzka DA, Pai RK, Rothenberg ME, Straumann A, Aceves SS, Alexander JA, Arva NC, Atkins D, Biedermann L, Blanchard C, Cianferoni A, Ciriza de Los Rios C, Clayton F, Davis CM, de Bortoli N, Dias JA, Falk GW, Genta RM, Ghaffari G, Gonsalves N, Greuter T, Hopp R, Hsu Blatman KS, Jensen ET, Johnston D, Kagalwalla AF, Larsson HM, Leung J, Louis H, Masterson JC, Menard-Katcher C, Menard-Katcher PA, Moawad FJ, Muir AB, Mukkada VA, Penagini R, Pesek RD, Peterson K, Putnam PE, Ravelli A, Savarino EV, Schlag C, Schreiner P, Simon D, Smyrk TC, Spergel JM, Taft TH, Terreehorst I, Vanuytsel T, Venter C, Vieira MC, Vieth M, Vlieg-Boerstra B, von Arnim U, Walker MM, Wechsler JB, Woodland P, Woosley JT, Yang GY, Zevit N, Safroneeva E. J Allergy Clin Immunol. 2022 Feb;149(2):659-670. doi: 10.1016/j.jaci.2021.07.001. Epub 2021 Jul 6.

Diagnostic merits of the Eosinophilic Esophagitis Diagnostic Panel from a single esophageal biopsy. Min S, Shoda T, Wen T, Rothenberg ME. J Allergy Clin Immunol. 2022 Feb;149(2):782-787.e1. doi: 10.1016/j.jaci.2021.07.032. Epub 2021 Aug 8.

Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis. Masuda MY, Barshow SM, Garg S, Putikova A, LeSuer WE, Alexander JA, Katzka DA, Dellon ES, Kita H, Horsley-Silva JL, Doyle AD, Wright BL. Clin Transl Gastroenterol. 2022 Nov 1;13(11):e00534. doi: 10.14309/ctg.0000000000000534.

Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry. Zevit N, Chehade M, Leung J, Marderfeld L, Dellon ES. J Allergy Clin Immunol Pract. 2022 Jan;10(1):143-149.e9. doi: 10.1016/j.jaip.2021.10.019. Epub 2021 Oct 22.

Eosinophilic gastrointestinal diseases make a name for themselves: A new consensus statement with updated nomenclature. Wright BL, Schwartz JT, Ruffner MA, Furuta GT, Gonsalves N, Dellon ES, Aceves SS. J Allergy Clin Immunol. 2022 Aug;150(2):291-293. doi: 10.1016/j.jaci.2022.05.012. Epub 2022 May 29. PMID: 35649464; PMCID: PMC9378528.

Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. Consensus recommendations have been developed for diagnosis of eosinophilic esophagitis (EoE), the most common EGID. However, there are currently no consensus guidelines for diagnosis of non-EoE EGIDs. Standardization of EGID terminology is one of the first priorities for developing these guidelines. In this study, a large group of researchers and clinicians aimed to reach international consensus for EGID nomenclature. The team used multiple rounds of surveys to develop a new tiered framework for EGID terms. Authors note that this revision of terms could advance both clinical care and research in EGIDs. Next steps include selection of specific disease markers and thresholds, definition of symptoms, exclusion of alternative diagnoses, and duration of disease.

Esophageal Manifestations of Dermatological Diseases, Diagnosis and Management. Arar AM, DeLay K, Leiman DA, Menard-Katcher P. Curr Treat Options Gastroenterol. 2022 Dec;20(4):513-528. doi: 10.1007/s11938-022-00399-6. Epub 2022 Oct 18.

Evaluating Eosinophilic Colitis as a Unique Disease using Colonic Molecular Profiles: A Multi-Site Study. Shoda T, Collins MH, Rochman M, Wen T, Caldwell JM, Mack LE, Osswald GA, Besse JA, Haberman Y, Aceves SS, Arva NC, Capocelli KE, Chehade M, Davis CM, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Klion A, Menard-Katcher C, Leung J, Mukkada V, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Denson LA, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR). Gastroenterology. 2022 Jan 24:S0016-5085(22)00038-5. doi: 10.1053/j.gastro.2022.01.022. Epub ahead of print. PMID: 35085569.

Eosinphilic colitis (EoC) has been a poorly understood condition with uncertainty whether it is a distinct disease or a manifestation of eosinophilic gastrointestinal disease or inflammatory bowel disease. Researchers from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) seeking to better understand the condition analyzed samples from more than 60 people treated at multiple medical centers v. controls to compare this rare disease to other conditions. They identified and analyzed 987 differentially expressed genes, established EoC transcriptomic profiles, identified mechanistic pathways, and compared findings with related conditions. They concluded that EoC is a distinct disease, establishing a basis for improved diagnosis and treatment.

Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis. Larey A, Aknin E, Daniel N, Osswald GA, Caldwell JM, Rochman M, Wasserman T, Collins MH, Arva NC, Yang GY, Rothenberg ME, Savir Y. Front Med (Lausanne). 2022 Oct 21;9:950728. doi: 10.3389/fmed.2022.950728. eCollection 2022.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods. Fulkerson PC, Lussier SJ, Bendixsen CG, Castina SM, Gebretsadik T, Marlin JS, Russell PB, Seibold MA, Everman JL, Moore CM, Snyder BM, Thompson K, Tregoning GS, Wellford S, Arbes SJ, Bacharier LB, Calatroni A, Camargo CA, Dupont WD, Furuta GT, Gruchalla RS, Gupta RS, Hershey GK, Jackson DJ, Johnson CC, Kattan M, Liu AH, Murrison L, Oâ Connor GT, Phipatanakul W, Rivera-Spoljaric K, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Hartert TV. medRxiv. 2022 Jul 10:2022.07.09.22277457. doi: 10.1101/2022.07.09.22277457. Preprint.

Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field. Rothenberg ME, Hottinger SKB, Gonsalves N, Furuta GT, Collins MH, Talley NJ, Peterson K, Menard-Katcher C, Smith M, Hirano I, Genta RM, Chehade M, Gupta SK, Spergel JM, Aceves SS, Dellon ES. J Allergy Clin Immunol. 2022 Mar;149(3):844-853. doi: 10.1016/j.jaci.2021.12.768. Epub 2021 Dec 22.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature. Dellon ES, Gonsalves N, Abonia JP, Alexander JA, Arva NC, Atkins D, Attwood SE, Auth MKH, Bailey DD, Biederman L, Blanchard C, Bonis PA, Bose P, Bredenoord AJ, Chang JW, Chehade M, Collins MH, Di Lorenzo C, Dias JA, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox AT, Genta RM, Greuter T, Gupta SK, Hirano I, Hiremath GS, Horsley-Silva JL, Ishihara S, Ishimura N, Jensen ET, Gutiérrez-Junquera C, Katzka DA, Khoury P, Kinoshita Y, Kliewer KL, Koletzko S, Leung J, Liacouras CA, Lucendo AJ, Martin LJ, McGowan EC, Menard-Katcher C, Metz DC, Miller TL, Moawad FJ, Muir AB, Mukkada VA, Murch S, Nhu QM, Nomura I, Nurko S, Ohtsuka Y, Oliva S, Orel R, Papadopoulou A, Patel DA, Pesek RD, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Ruffner MA, Safroneeva E, Schreiner P, Schoepfer A, Schroeder SR, Shah N, Souza RF, Spechler SJ, Spergel JM, Straumann A, Talley NJ, Thapar N, Vandenplas Y, Venkatesh RD, Vieira MC, von Arnim U, Walker MM, Wechsler JB, Wershil BK, Wright BL, Yamada Y, Yang GY, Zevit N, Rothenberg ME, Furuta GT, Aceves SS. Clin Gastroenterol Hepatol. 2022 Feb 16:S1542-3565(22)00143-4. doi: 10.1016/j.cgh.2022.02.017. Online ahead of print.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis. Safroneeva E, Pan Z, King E, Martin LJ, Collins MH, Yang GY, Capocelli KE, Arva NC, Abonia JP, Atkins D, Bonis PA, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Schoepfer AM, Spergel JM, Wershil BK, Rothenberg ME, Aceves SS, Furuta GT; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Clin Gastroenterol Hepatol. 2022 Apr;20(4):766-775.e4. doi: 10.1016/j.cgh.2021.05.049. Epub 2021 May 29.

Mast cell-pain connection in eosinophilic esophagitis. Zhang S, Shoda T, Aceves SS, Arva NC, Chehade M, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Leung J, Spergel AKR, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group. Allergy. 2022 Jun;77(6):1895-1899. doi: 10.1111/all.15260. Epub 2022 Mar 3.

Multiancestral polygenic risk score for pediatric asthma. Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, Jarvik GP, Kiryluk K, Kullo IJ, Liu C, Luo Y, Satterfield BA, Smoller JW, Walunas TL, Connolly J, Sleiman P, Mersha TB, Mentch FD, Hakonarson H, Prows CA, Biagini JM, Khurana Hershey GK, Martin LJ, Kottyan L; eMERGE Network. J Allergy Clin Immunol. 2022 Nov;150(5):1086-1096. doi: 10.1016/j.jaci.2022.03.035. Epub 2022 May 18.

Posttreatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis. Ruffner MA, Cotton CC, Dellon ES. Am J Gastroenterol. 2022 Sep 1;117(9):1519-1522. doi: 10.14309/ajg.0000000000001802. Epub 2022 Apr 26.

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort. Hirano I, Collins MH, King E, Sun Q, Chehade M, Abonia JP, Bonis PA, Capocelli KE, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Leung J, Katzka D, Menard-Katcher P, Khoury P, Klion A, Mukkada VA, Peterson K, Rudman-Spergel AK, Spergel JA, Yang GY, Rothenberg ME, Aceves SS, Furuta GT. Am J Gastroenterol. 2022 Jan 20. doi: 10.14309/ajg.0000000000001625. Epub ahead of print. PMID: 35080202.

Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach that occurs when certain white blood cells known as eosinophils gather in large numbers in the stomach, causing injury and irritation. In this study, researchers aimed to better understand the endoscopic manifestations of EG and develop a standardized instrument for investigations. Using data prospectively collected as part of CEGIR, the team evaluated endoscopic features of children and adults with EG recorded with the EG Endoscopic Reference System (EG-REFS). Researchers identified a strong correlation between EG-REFS scores and physician global assessment of endoscopy severity. EG-REFS severity was significantly correlated with active histology and a tendency for the gastric antrum (lower portion of the stomach). The authors note that further development of EG-REFS should improve its utility in clinical studies.

Provider Beliefs, Practices, and Perceived Barriers to Dietary Elimination Therapy in Eosinophilic Esophagitis. Chang JW, Kliewer K, Katzka DA, Peterson KA, Gonsalves N, Gupta SK, Furuta GT, Dellon ES. Am J Gastroenterol. 2022 Dec 1;117(12):2071-2074. doi: 10.14309/ajg.0000000000001988. Epub 2022 Sep 1. PMID: 36066475; PMCID: PMC9722505.

Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. This immune response can occur as a reaction to certain foods. Although effective dietary treatments are often available, physicians tend to prefer medications. In this study, researchers assessed providers’ perceptions of EoE dietary therapy, including effectiveness, practice patterns, and barriers. The team collected this data through a web-based survey of providers. Results show that providers view diet as the least effective treatment for EoE. Barriers to treatment include the belief that patients are disinterested and unlikely to adhere. In addition, providers indicated that with less access to dietitians, nonacademic providers often manage diets without dietitian guidance. As patients are often highly accepting of diets and multiple treatment options for EoE, authors state that clinicians need evidence-based knowledge on EoE diets, access to dietitians, and awareness of patient preferences.

Refractory eosinophilic esophagitis: what to do when the patient has not responded to proton pump inhibitors, steroids and diet. Strauss AL, Falk GW. Curr Opin Gastroenterol. 2022 Jul 1;38(4):395-401. doi: 10.1097/MOG.0000000000000842.

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study. Seibold MA, Moore CM, Everman JL, Williams BJM, Nolin JD, Fairbanks-Mahnke A, Plender EG, Patel BB, Arbes SJ, Bacharier LB, Bendixsen CG, Calatroni A, Camargo CA Jr, Dupont WD, Furuta GT, Gebretsadik T, Gruchalla RS, Gupta RS, Khurana Hershey GK, Murrison LB, Jackson DJ, Johnson CC, Kattan M, Liu AH, Lussier SJ, O'Connor GT, Rivera-Spoljaric K, Phipatanakul W, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Fulkerson PC, Hartert TV; HEROS study team. J Allergy Clin Immunol. 2022 Aug;150(2):302-311. doi: 10.1016/j.jaci.2022.05.014. Epub 2022 Jun 1. PMID: 35660376; PMCID: PMC9155183.

Children and people with asthma or other allergic diseases are typically known as high-risk groups for many respiratory viruses. However, it is currently unknown whether these groups are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection. In this study, researchers aimed to determine the incidence of SARS-CoV-2 infection in households with children, as well as whether self-reported asthma or other allergic diseases are associated with infection and household transmission. Participants included allergic disease patients from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), which provided an accessible cohort for the study. For six months, the team collected biweekly nasal swabs and weekly surveys to calculate the probabilities of infection and transmission. Researchers then used regression analyses to determine associated risk factors. Results suggest that asthma does not increase the risk of SARS-CoV-2 infection. Food allergy was associated with lower infection risk, while body mass index was associated with increased infection risk. Authors note that understanding how these factors modify infection risk may offer new avenues for preventing infection.

Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. Rothenberg ME. J Allergy Clin Immunol. 2022 Dec;150(6):1325-1332. doi: 10.1016/j.jaci.2022.09.027. Epub 2022 Oct 6.

Should We Pretreat Before We Go Nuts? Antihistamines Modestly Reduce the Side Effects of Peanut Oral Immunotherapy. Wright BL. J Allergy Clin Immunol Pract. 2022 Sep;10(9):2395-2396. doi: 10.1016/j.jaip.2022.06.015.

What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities. Chang JW, Chen VL, Rubenstein JH, Dellon ES, Wallner LP, De Vries R. Dis Esophagus. 2022 Jun 15;35(6):doab073. doi: 10.1093/dote/doab073. PMID: 34718475.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that damages the esophagus. Little is known about how patients with EoE experience their symptoms, receive care, and cope with their disease. Often, patients seek peer support from online communities. As an unfiltered source of patient perspectives, these communities can provide insights on unmet needs and barriers to care. In this study, researchers performed a qualitative analysis of electronic health forums to characterize patient-to-patient conversations about EoE symptoms and the experience of disease. The team analyzed a random sample of conversation threads from three publicly accessible electronic health forums hosting EoE communities. Results showed that patients with EoE interpret their disease as sporadic events and lack reliable sources of knowledge, which may influence how they prioritize treatment. Authors note that providers should equip themselves with evidence-based knowledge, engage in shared decision-making, and look outside of clinical settings in order to recognize barriers to disease management.

A Gut-Wrenching Case of Hypereosinophilia. Melethil S, Abonia JP. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3524-3525. doi: 10.1016/j.jaip.2021.05.039. PMID: 34507713.

In a case study of hypereosinophilia, an allergic inflammatory condition in which white blood cells called eosinophils are at high levels in the body, a pediatric patient had recurrent gastrointestinal symptoms and histology showing elevated eosinophils in biopsy specimens. After excluding secondary causes of gastrointestinal eosinophilia, the clinicians diagnosed the patient with eosinophilic gastroenteritis (EGE). Eosinophilic gastritis (EG) and EGE are a heterogeneous group of rare disorders due to selective eosinophilic infiltration causing inflammation in the stomach and small intestine, in the absence of other secondary causes of eosinophilia. The exact incidence is unknown but is more commonly diagnosed in children younger than 5 years. In adults, the peak age of diagnosis is in the third decade of life. Authors say this case exemplifies two key points for healthcare providers: 1) Refer patients presenting with peripheral eosinophilia and recurrent or persistent gastrointestinal (GI) symptoms for evaluation for an intestinal biopsy and 2) Recognize that eosinophilic gastrointestinal diseases can be diagnosed only after other secondary causes of eosinophilia like parasitic infections or drug-induced causes are ruled out.

A Single-Food Milk Elimination Diet Is Effective for Treatment of Eosinophilic Esophagitis in Children. Wechsler JB, Schwartz S, Arva NC, Kim KA, Chen L, Makhija M, Amsden K, Keeley K, Mohammed S, Dellon ES, Kagalwalla AF. Clin Gastroenterol Hepatol. 2021 Apr 3:S1542-3565(21)00384-0. doi: 10.1016/j.cgh.2021.03.049. Online ahead of print.

Comorbid Diagnosis of Eosinophilic Esophagitis and Inflammatory Bowel Disease in the Pediatric Population. Moore H, Wechsler J, Frost C, Whiteside E, Baldassano R, Markowitz J, Muir AB. J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):398-403. doi: 10.1097/MPG.0000000000003002.

Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee. Zimmermann N, Abonia JP, Dreskin SC, Akin C, Bolton S, Happel CS, Geller M, Larenas-Linnemann D, Nanda A, Peterson K, Wasan A, Wechsler J, Zhang S, Bernstein JA. J Allergy Clin Immunol. 2021 Oct;148(4):964-983. doi: 10.1016/j.jaci.2021.06.030. Epub 2021 Aug 9. PMID: 34384610.

In human tissue biopsies, mast cells and eosinophils are commonly found. However, for several clinical conditions, there are knowledge gaps in determining diagnostic thresholds and how samples are processed, interpreted, and reported. These discrepancies can delay the correct diagnosis of a patient’s condition. A work group of pathology, allergy, dermatology, hematology/oncology, and gastroenterology stakeholders assembled to address this need. Together, the group developed a standardized approach for assessing mast cells and eosinophils in skin, gastrointestinal, and bone marrow pathologic specimens for the benefit of clinical practice and patients.

Diagnosis of Pediatric Non-Esophageal Eosinophilic Gastrointestinal Disorders by Eosinophil Peroxidase Immunohistochemistry. Hasan SH, Taylor S, Garg S, Buras MR, Doyle AD, Bauer CS, Wright BL, Schroeder S. Pediatr Dev Pathol. 2021 Nov-Dec;24(6):513-522. doi: 10.1177/10935266211024552. Epub 2021 Jun 28.

Distance to pediatric gastroenterology providers is associated with decreased diagnosis of eosinophilic esophagitis in rural populations. McGowan EC, Keller JP, Muir AB, Dellon ES, Peng R, Keet CA, Jensen ET. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4489-4492.e2. doi: 10.1016/j.jaip.2021.08.034. Epub 2021 Sep 14. PMID: 34534720; PMCID: PMC8671202.

Eosinophilic esophagitis (EoE) is characterized by immune cells called eosinophils building up in the esophagus, which may cause polyps, tissue break down, inflammation, and ulcers. In this cross-sectional study, researchers examined data from children enrolled in Medicaid 2012. They found that the apparent lower prevalence of eosinophilic esophagitis in rural communities was attenuated when adjusting for distance to provider. These results suggest that diagnostic disparities likely exist for eosinophilic esophagitis among children residing in rural areas.

Do rural health disparities affect prevalence data in pediatric eosinophilic esophagitis?. Sabet C, Klion AD, Bailey D, Jensen E, Chehade M, Abonia JP, Rothenberg ME, Furuta GT, Muir AB; CEGIR Investigator Group. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2549-2551. doi: 10.1016/j.jaip.2021.03.027.

Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood. Dellon ES, Shaheen O, Koutlas NT, Chang AO, Martin LJ, Rothenberg ME, Jensen ET. Dis Esophagus. 2021 Feb 10;34(2):doaa074. doi: 10.1093/dote/doaa074.

Effect of topical swallowed steroids on the bacterial and fungal esophageal microbiota in eosinophilic esophagitis. Benitez AJ, Tanes C, Mattei L, Hofstaedter CE, Kim DK, Gross J, Ruffner MA, Albenberg L, Spergel J, Bittinger K, Muir AB. Allergy. 2021 May;76(5):1549-1552. doi: 10.1111/all.14602. Epub 2020 Oct 19.

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies. Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ, Pavord ID, Akuthota P, Roufosse F, Rothenberg ME. Annu Rev Immunol. 2021 Apr 26;39:719-757. doi: 10.1146/annurev-immunol-093019-125918. Epub 2021 Mar 1.

Eosinophilic Esophagitis: A Review. Muir A, Falk GW. JAMA. 2021 Oct 5;326(13):1310-1318. doi: 10.1001/jama.2021.14920.

Researchers affiliated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) have published a new review paper examining eosinophilic esophagitis (EoE), an allergic inflammatory disease. EoE is characterized by elevated eosinophils (a type of disease-fighting white blood cell) in the esophagus (the tube connecting the mouth to the stomach). It affects an estimated 34.4/100,000 people in Europe and North America, including both children and adults. To diagnose the disease and evaluate treatment efficacy, a doctor inserts a thin, flexible tube with a light and camera at the end through a patient’s mouth, into the stomach, and sometimes into the upper intestine and collects tissue samples. In this paper, researchers discuss symptoms of the disease along with genetic and environmental factors associated with it. They also examine several current therapies, including proton pump inhibitors, topical steroid preparations, dietary therapy, and endoscopic dilation, and summarize recent systematic reviews of therapy trials.

Eosinophilic esophagitis may persist after discontinuation of oral immunotherapy. Hamant L, Freeman C, Garg S, Wright BL, Schroeder S. Ann Allergy Asthma Immunol. 2021 Mar;126(3):299-302. doi: 10.1016/j.anai.2020.12.007. Epub 2020 Dec 17.

How to approach adult patients with asymptomatic esophageal eosinophilia. Schreiner P, Biedermann L, Greuter T, Wright BL, Straumann A. Dis Esophagus. 2021 Jan 11;34(1):doaa105. doi: 10.1093/dote/doaa105.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk. Shoda T, Wen T, Caldwell JM, Ben-Baruch Morgenstern N, Osswald GA, Rochman M, Mack LE, Felton JM, Abonia JP, Arva NC, Atkins D, Bonis PA, Capocelli KE, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Putnam PE, Rudman Spergel AK, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group. Gastroenterology. 2022 Feb;162(2):439-453. doi: 10.1053/j.gastro.2021.10.016. Epub 2021 Oct 21. PMID: 34687736; PMCID: PMC8792211.

Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated immunologic disease that can progress to fibrostenosis, but the molecular pathogenesis of fibrostenotic EoE is not well understood. This study found that endothelial TSPAN12 contributes to fibrostenotic EoE and is the first molecular correlate of esophageal diameter. These findings provide new insight into previously underrecognized roles of the endothelium in disease pathogenesis. Anti–IL-13 therapy may improve fibrostenotic EoE through normalizing TSPAN12 levels.

Motivations, Barriers, and Outcomes of Patient-Reported Shared Decision Making in Eosinophilic Esophagitis. Chang JW, Rubenstein JH, Mellinger JL, Kodroff E, Strobel MJ, Scott M, Mack D, Book W, Sable K, Kyle S, Paliana A, Dellon ES. Dig Dis Sci. 2021 Jun;66(6):1808-1817. doi: 10.1007/s10620-020-06438-5. Epub 2020 Jul 3.

Moving FORWARD Toward Racial Equity in Food Allergy. Davis CM. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2874-2875. doi: 10.1016/j.jaip.2021.04.066.

Noninvasive biomarkers identify eosinophilic esophagitis: A prospective longitudinal study in children. Wechsler JB, Ackerman SJ, Chehade M, Amsden K, Riffle ME, Wang MY, Du J, Kleinjan ML, Alumkal P, Gray E, Kim KA, Wershil BK, Kagalwalla AF. Allergy. 2021 Apr 27. doi: 10.1111/all.14874. Online ahead of print.

Patients with eosinophilic gastrointestinal disorders have lower in-hospital mortality rates related to COVID-19. Qeadan F, Chehade M, Tingey B, Egbert J, Dellon ES, Peterson KA. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4473-4476.e4. doi: 10.1016/j.jaip.2021.09.022. Epub 2021 Sep 23. PMID: 34563741; PMCID: PMC8459462.

Little is known about eosinophilic gastrointestinal disease (EGID) and COVID-19 outcomes. By reducing viral entry into cells, the mucosal responses of patients with EGID may protect against severe effects of COVID-19. In this study, researchers compared hospitalization rates, ventilator dependence, and death between patients with and without EGID. When compared with non–EGID COVID-19 positive patients, they found that EGID COVID-19 positive individuals stayed longer in the hospital, yet had lower rates of inpatient mortality. This analysis suggests that EGID may provide a protective effect against severe COVID-19 outcomes. In future studies, researchers plan to further explore the protective role of reduced expression of ACE2/TMPRSS2 and the eosinophilic disease itself in COVID-19 mortality.

RNA sequencing identifies global transcriptional changes in peripheral CD4(+) cells during active oesophagitis and following epicutaneous immunotherapy in eosinophilic oesophagitis. Ruffner MA, Zhang Z, Maurer K, Muir AB, Cianferoni A, Sullivan KE, Spergel JM. Clin Transl Immunology. 2021 Jul 22;10(7):e1314. doi: 10.1002/cti2.1314. eCollection 2021.

Treatment of Eosinophilic Esophagitis: Diet or Medication?. Chehade M, Aceves SS. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3249-3256. doi: 10.1016/j.jaip.2021.07.029. PMID: 34507706.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease characterized by elevated eosinophils (white blood cells) in the esophagus (the tube connecting the mouth to the stomach). The prevalence of EoE is increasing in children and adults. As a chronic condition currently without a cure, EoE must be carefully managed to prevent complications, such as food impactions in the esophagus or narrowing of the lumen. In this paper, researchers discuss the current approaches for dietary and pharmacologic management of EoE and the need for future clinical trials to help tailor therapies to individual patients with this chronic disease.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders. Chiang AWT, Duong LD, Shoda T, Nhu QM, Ruffner M, Hara T, Aaron B, Joplin E, Manresa MC, Abonia JP, Dellon ES, Hirano I, Gonsalves N, Gupta SK, Furuta GT, Rothenberg ME, Lewis NE, Muir AB, Aceves SS; CEGIR Investigator Group. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):718-722. doi: 10.1097/MPG.0000000000003032.

Eosinophilic gastrointestinal disorders are inflammatory conditions caused by chronic type 2 (T2) inflammation. In this study, researchers sought to better understand the impact of this T2 inflammation on susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus-induced disease 2019 (COVID-19). Researchers analyzed gene expression data in pediatric eosinophilic esophagitis, eosinophilic gastritis, and in normal adults using publicly available datasets. They concluded that eosinophilic gastrointestinal diseases are not risk factors for COVID-19. and that T2 immunity & pediatric age could be protective for SARS-CoV-2 infection in the GI tract.

Unsedated transnasal esophagoscopy with virtual reality distraction enables earlier monitoring of dietary therapy in eosinophilic esophagitis. Friedlander JA, Fleischer DM, Black JO, Levy M, Rothenberg ME, Smith C, Nguyen N, Pan Z, Furuta GT. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3494-3496. doi: 10.1016/j.jaip.2021.06.030. Epub 2021 Jul 2. PMID: 34224927; PMCID: PMC8459391.

Eosinophilic esophagitis is a chronic, inflammatory disease of the esophagus often treated with an elimination diet, where patients avoid specific foods that are triggering the disease. The current standard of care for diagnosis and symptom monitoring requires repeated sedated endoscopy procedures over time. After the initial diagnostic endoscopy, many assessments may be needed to establish the correct diet. For patients, these repeated diagnostic procedures raise issues of risk, cost, and lost time from school and/or work. They also extend the time patients must wait to reintroduce foods. In this study, researchers seeking to address these concerns tested the use of an emerging technology, less invasive monitoring approach compared with standard endoscopy—unsedated transnasal esophagoscopy (TN-Eso) with virtual reality distraction. Although this was a pilot study involving only five patients, the researchers found that TN-Eso was well-tolerated and preferred by patients and families. Tests using the new technology detected the return of esophagitis as soon as two weeks after single-food exposure, suggesting that the timing of food reintroductions could be shortened by 50% to 75%, compared with the traditional endoscopies (which typically occur at 12-week intervals). Study authors say these findings support a shortened challenge period with the use of TN-Eso, which may lead to faster identification of a suitable treatment. The study also demonstrates that food allergen-induced eosinophilic esophagitis occurs within two weeks following exposure to the triggering food.

Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis. Joshi S, Rubenstein JH, Dellon ES, Worthing N, Stefanadis Z, Chang JW. Am J Gastroenterol. 2021 Jun 1;116(6):1336-1338. doi: 10.14309/ajg.0000000000001170.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Hirano I, Chan ES, Rank MA, Sharaf RN, Stollman NH, Stukus DR, Wang K, Greenhawt M, Falck-Ytter YT; AGA Institute Clinical Guidelines Committee; Joint Task Force on Allergy-Immunology Practice Parameters. Gastroenterology. 2020 May;158(6):1776-1786. doi: 10.1053/j.gastro.2020.02.038.

AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Hirano I, Chan ES, Rank MA, Sharaf RN, Stollman NH, Stukus DR, Wang K, Greenhawt M, Falck-Ytter YT; AGA Institute Clinical Guidelines Committee; Joint Task Force on Allergy-Immunology Practice Parameters. Ann Allergy Asthma Immunol. 2020 May;124(5):416-423. doi: 10.1016/j.anai.2020.03.020.

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Aceves S, Collins MH, Rothenberg ME, Furuta GT, Gonsalves N; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jan;145(1):28-37. doi: 10.1016/j.jaci.2019.11.012. Epub 2019 Nov 20.

Antifibrotic Effects of the Thiazolidinediones in Eosinophilic Esophagitis Pathologic Remodeling: A Preclinical Evaluation. Nhu QM, Hsieh L, Dohil L, Dohil R, Newbury RO, Kurten R, Moawad FJ, Aceves SS. Clin Transl Gastroenterol. 2020 Apr;11(4):e00164. doi: 10.14309/ctg.0000000000000164.

Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. Hirano I, Furuta GT. Gastroenterology. 2020 Mar;158(4):840-851. doi: 10.1053/j.gastro.2019.09.052. Epub 2019 Dec 10.

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders. Pesek RD, Reed CC, Collins MH, Muir AB, Fulkerson PC, Menard-Katcher C, Falk GW, Kuhl J, Magier AZ, Ahmed FN, Demarshall M, Gupta A, Gross J, Ashorobi T, Carpenter CL, Krischer JP, Gonsalves N, Hirano I, Spergel JM, Gupta SK, Furuta GT, Rothenberg ME, Dellon ES; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Dig Dis Sci. 2020 Jul;65(7):2024-2035. doi: 10.1007/s10620-019-05961-4. Epub 2019 Nov 26.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study. Greuter T, Godat A, Ringel A, Almonte HS, Schupack D, Mendoza G, McCright-Gill T, Dellon ES, Hirano I, Alexander J, Chehade M, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Schoepfer AM, Straumann A, Katzka DA. Clin Gastroenterol Hepatol. 2020 Aug 13:S1542-3565(20)31136-8. doi: 10.1016/j.cgh.2020.08.027. Online ahead of print.

Elimination diets for eosinophilic esophagitis: making the best choice. Chehade M, Brown S. Expert Rev Clin Immunol. 2020 Jul;16(7):679-687. doi: 10.1080/1744666X.2020.1801419. Epub 2020 Aug 4.

Emerging therapies for eosinophilic esophagitis. Greuter T, Hirano I, Dellon ES. J Allergy Clin Immunol. 2020 Jan;145(1):38-45. doi: 10.1016/j.jaci.2019.10.027. Epub 2019 Nov 6.

EoE disease monitoring: Where we are and where we are going. Godwin B, Wilkins B, Muir AB. Ann Allergy Asthma Immunol. 2020 Mar;124(3):240-247. doi: 10.1016/j.anai.2019.12.004. Epub 2019 Dec 9.

Eosinophilic Esophagitis: Existing and Upcoming Therapies in an Age of Emerging Molecular and Personalized Medicine. Slack IF, Schwartz JT, Mukkada VA, Hottinger S, Abonia JP. Curr Allergy Asthma Rep. 2020 Jun 6;20(8):30. doi: 10.1007/s11882-020-00928-2.

Eosinophilic gastrointestinal disease below the belt. Pesek RD, Rothenberg ME. J Allergy Clin Immunol. 2020 Jan;145(1):87-89.e1. doi: 10.1016/j.jaci.2019.10.013. Epub 2019 Oct 24.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Doyle AD, Masuda MY, Kita H, Wright BL. Front Immunol. 2020 Dec 1;11:603295. doi: 10.3389/fimmu.2020.603295. eCollection 2020.

Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort. Dunn JLM, Shoda T, Caldwell JM, Wen T, Aceves SS, Collins MH, Dellon ES, Falk GW, Leung J, Martin LJ, Menard-Katcher P, Rudman-Spergel AK, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jun;145(6):1629-1640.e4. doi: 10.1016/j.jaci.2020.01.051. Epub 2020 Mar 19.

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases. Jensen ET, Aceves SS, Bonis PA, Bray K, Book W, Chehade M, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Katzka DA, Kyle S, Mack D, Kodroff E, Leung J, Mukkada VA, Scott M, Paliana A, Sable K, Spergel JM, Strobel MJ, Krischer J, Rothenberg ME, Abonia P; CEGIR Investigator group. J Pediatr Gastroenterol Nutr. 2020 Oct;71(4):524-529. doi: 10.1097/MPG.0000000000002817.

Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Bolton SM, Kagalwalla AF, Arva NC, Wang MY, Amsden K, Melin-Aldana H, Dellon ES, Bryce PJ, Wershil BK, Wechsler JB. Am J Gastroenterol. 2020 Feb;115(2):224-233. doi: 10.14309/ajg.0000000000000474.

Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in adults. Greuter T, Straumann A. Allergy. 2020 Mar;75(3):727-730. doi: 10.1111/all.14112. Epub 2019 Dec 5.

Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in children. Spergel JM, Brown-Whitehorn TA, Muir A, Liacouras CA. Allergy. 2020 Jun;75(6):1522-1524. doi: 10.1111/all.14188. Epub 2020 Jan 31.

Modeling Epithelial Homeostasis and Reactive Epithelial Changes in Human and Murine Three-Dimensional Esophageal Organoids. Nakagawa H, Kasagi Y, Karakasheva TA, Hara T, Aaron B, Shimonosono M, Kijima T, Giroux V, Bailey D, Wilkins B, Abrams JA, Falk GW, Aceves SS, Spergel JM, Hamilton KE, Whelan KA, Muir AB. Curr Protoc Stem Cell Biol. 2020 Mar;52(1):e106. doi: 10.1002/cpsc.106.

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study. Shoda T, Wen T, Caldwell JM, Collins MH, Besse JA, Osswald GA, Abonia JP, Arva NC, Atkins D, Capocelli KE, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Mukkada VA, Putnam PE, Sheridan RM, Rudman Spergel AK, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2020 Jan;145(1):255-269. doi: 10.1016/j.jaci.2019.11.007. Epub 2019 Nov 16.

Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis. Whelan KA, Godwin BC, Wilkins B, Elci OU, Benitez A, DeMarshall M, Sharma M, Gross J, Klein-Szanto AJ, Liacouras CA, Dellon ES, Spergel JM, Falk GW, Muir AB, Nakagawa H. Clin Gastroenterol Hepatol. 2020 Jun;18(7):1475-1482.e1. doi: 10.1016/j.cgh.2019.08.055. Epub 2019 Sep 6.

Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters. Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES; AGA Institute. Electronic address: clinicalpractice@gastro.org; Joint Task Force on Allergy-Immunology Practice Parameters collaborators. Electronic address: drdanawallace@gmail.com; AGA Institute; Joint Task Force on Allergy-Immunology Practice Parameters collaborators. Gastroenterology. 2020 May;158(6):1789-1810.e15. doi: 10.1053/j.gastro.2020.02.039.

Technical review on the management of eosinophilic esophagitis: a report from the AGA institute and the joint task force on allergy-immunology practice parameters. Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES; AGA Institute Electronic address: clinicalpractice@gastroorg; Joint Task Force on Allergy-Immunology Practice Parameters collaborators Electronic address: drdanawallace@gmailcom; AGA Institute; Joint Task Force on Allergy-Immunology Practice Parameters collaborators. Ann Allergy Asthma Immunol. 2020 May;124(5):424-440.e17. doi: 10.1016/j.anai.2020.03.021.

The genetic etiology of eosinophilic esophagitis. Kottyan LC, Parameswaran S, Weirauch MT, Rothenberg ME, Martin LJ. J Allergy Clin Immunol. 2020 Jan;145(1):9-15. doi: 10.1016/j.jaci.2019.11.013.

The potential for malignancy from atopic disorders and allergic inflammation: A systematic review and meta-analysis. Muir AB, Whelan KA, Dougherty MK, Aaron B, Navarre B, Aceves SS, Dellon ES, Jensen ET. Clin Exp Allergy. 2020 Feb;50(2):147-159. doi: 10.1111/cea.13537. Epub 2019 Dec 20.

The role of eosinophils in immunotherapy. Cafone J, Ruffner MA, Spergel JM. Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):329. doi: 10.1097/ACI.0000000000000617.

Unanswered questions in eosinophilic esophagitis. Nhu QM, Aceves SS. Ann Allergy Asthma Immunol. 2020 Mar;124(3):227-228. doi: 10.1016/j.anai.2019.12.003. Epub 2019 Dec 9.

Validation of self-reported diagnosis of eosinophilic gastrointestinal disorders patients enrolled in the CEGIR contact registry. Hiremath G, Krischer JP, Rothenberg ME, Dellon ES. Clin Res Hepatol Gastroenterol. 2020 Nov 5:101555. doi: 10.1016/j.clinre.2020.10.001. Online ahead of print.

A Comparative Analysis of Eating Behavior of School-Aged Children with Eosinophilic Esophagitis and Their Caregivers' Quality of Life: Perspectives of Caregivers. Hiremath G, Rogers E, Kennedy E, Hemler J, Acra S. Dysphagia. 2019 Aug;34(4):567-574. doi: 10.1007/s00455-019-09984-x. Epub 2019 Feb 2.

A Conceptual Approach to Understanding Treatment Response in Eosinophilic Esophagitis. Dellon ES, Gupta SK. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2149-2160. doi: 10.1016/j.cgh.2019.01.030. Epub 2019 Jan 30.

Climbing New Mountains: How Antibodies Blocking α4β7 Integrins Tamed Eosinophilic Inflammation of the Intestinal Tract. Olbrich CL, Simerly L, de Zoeten EF, Furuta GT, Spencer LA. Dig Dis Sci. 2019 Aug;64(8):2068-2071. doi: 10.1007/s10620-019-05706-3.

Consortium of Eosinophilic Gastrointestinal Disease Researchers: Advancing the Field of Eosinophilic GI Disorders Through Collaboration. Gupta SK, Falk GW, Aceves SS, Chehade M, Collins MH, Dellon ES, Gonsalves N, Hirano I, Mukkuda VA, Peterson KA, Spergel J, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Gastroenterology. 2019 Mar;156(4):838-842. doi: 10.1053/j.gastro.2018.10.057. Epub 2018 Nov 17.

Cost-effective care in eosinophilic esophagitis. Dellon ES. Ann Allergy Asthma Immunol. 2019 Aug;123(2):166-172. doi: 10.1016/j.anai.2019.04.010. Epub 2019 Apr 19.

Editorial: the evolving epidemiology of EoE-up, up, and away?. Dellon ES. Aliment Pharmacol Ther. 2019 Jun;49(11):1448-1449. doi: 10.1111/apt.15252.

Eosinophil progenitor levels correlate with tissue pathology in pediatric eosinophilic esophagitis. Schwartz JT, Morris DW, Collins MH, Rothenberg ME, Fulkerson PC. J Allergy Clin Immunol. 2019 Mar;143(3):1221-1224.e3. doi: 10.1016/j.jaci.2018.10.036. Epub 2018 Nov 9.

Eosinophilic esophagitis during sublingual and oral allergen immunotherapy. Cafone J, Capucilli P, Hill DA, Spergel JM. Curr Opin Allergy Clin Immunol. 2019 Aug;19(4):350-357. doi: 10.1097/ACI.0000000000000537.

Eosinophilic esophagitis: early diagnosis is the key. Muir AB, Brown-Whitehorn T, Godwin B, Cianferoni A. Clin Exp Gastroenterol. 2019 Aug 15;12:391-399. doi: 10.2147/CEG.S175061. eCollection 2019.

Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis. Masterson JC, Biette KA, Hammer JA, Nguyen N, Capocelli KE, Saeedi BJ, Harris RF, Fernando SD, Hosford LB, Kelly CJ, Campbell EL, Ehrentraut SF, Ahmed FN, Nakagawa H, Lee JJ, McNamee EN, Glover LE, Colgan SP, Furuta GT. J Clin Invest. 2019 Jul 2;129(8):3224-3235. doi: 10.1172/JCI126744. eCollection 2019 Jul 2.

Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis. Muir AB, Wang JX, Nakagawa H. J Gastroenterol. 2019 Jan;54(1):10-18. doi: 10.1007/s00535-018-1498-3. Epub 2018 Aug 12.

Feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders. Chehade M, Meyer R, Beauregard A. Ann Allergy Asthma Immunol. 2019 Jun;122(6):603-609. doi: 10.1016/j.anai.2019.03.020. Epub 2019 Mar 26.

Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α. Kasagi Y, Dods K, Wang JX, Chandramouleeswaran PM, Benitez AJ, Gambanga F, Kluger J, Ashorobi T, Gross J, Tobias JW, Klein-Szanto AJ, Spergel JM, Cianferoni A, Falk GW, Whelan KA, Nakagawa H, Muir AB. J Allergy Clin Immunol. 2019 Jul;144(1):171-182. doi: 10.1016/j.jaci.2018.10.067. Epub 2018 Dec 20.

Histologic similarities in children with eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. Nguyen N, Baumgarten A, Wright BL, Capocelli KE, Pan Z, Lee JJ, Furuta GT, Masterson JC. J Allergy Clin Immunol. 2019 Mar;143(3):1237-1240.e2. doi: 10.1016/j.jaci.2018.10.047. Epub 2018 Nov 14.

How to Advance Research, Education, and Training in the Study of Rare Diseases. Groft SC, Gopal-Srivastava R, Dellon ES, Gupta SK. Gastroenterology. 2019 Oct;157(4):917-921. doi: 10.1053/j.gastro.2019.08.010. Epub 2019 Aug 8.

Illuminating Elimination Diets: Controversies Regarding Dietary Treatment of Eosinophilic Esophagitis. Cotton CC, Durban R, Dellon ES. Dig Dis Sci. 2019 Jun;64(6):1401-1408. doi: 10.1007/s10620-019-05602-w.

Immunology of the ancestral differences in eosinophilic esophagitis. Kottyan L, Spergel JM, Cianferoni A. Ann Allergy Asthma Immunol. 2019 May;122(5):443-444. doi: 10.1016/j.anai.2018.10.026. Epub 2018 Nov 7.

Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium. Pesek RD, Reed CC, Muir AB, Fulkerson PC, Menard-Katcher C, Falk GW, Kuhl J, Martin EK, Magier AZ, Ahmed F, Demarshall M, Gupta A, Gross J, Ashorobi T, Carpenter CL, Krischer JP, Gonsalves N, Spergel JM, Gupta SK, Furuta GT, Rothenberg ME, Dellon ES; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Am J Gastroenterol. 2019 Jun;114(6):984-994. doi: 10.14309/ajg.0000000000000228.

Mechanisms of gastrointestinal allergic disorders. Azouz NP, Rothenberg ME. J Clin Invest. 2019 Mar 11;129(4):1419-1430. doi: 10.1172/JCI124604. eCollection 2019 Mar 11.

Minimally symptomatic patients with eosinophilic esophagitis should still be actively treated-PRO. Muir A, Moore H, Spergel JM. Ann Allergy Asthma Immunol. 2019 Jun;122(6):572-573. doi: 10.1016/j.anai.2018.09.468. Epub 2018 Oct 5.

New Developments in the Diagnosis and Treatment of Eosinophilic Esophagitis. Nhu QM, Moawad FJ. Curr Treat Options Gastroenterol. 2019 Mar;17(1):48-62. doi: 10.1007/s11938-019-00216-7.

No Maintenance, No Gain in Long-term Treatment of Eosinophilic Esophagitis. Dellon ES. Clin Gastroenterol Hepatol. 2019 Feb;17(3):397-399. doi: 10.1016/j.cgh.2018.07.038.

Overestimation of the diagnosis of eosinophilic colitis with reliance on billing codes. Muir AB, Jensen ET, Wechsler JB, Menard-Katcher P, Falk GW, Aceves SS, Furuta GT, Dellon ES, Rothenberg ME, Spergel JM. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2434-2436. doi: 10.1016/j.jaip.2019.03.020. Epub 2019 Mar 25.

Prevalence of eosinophilic colitis and the diagnoses associated with colonic eosinophilia. DiTommaso LA, Rosenberg CE, Eby MD, Tasco A, Collins MH, Lyles JL, Putnam PE, Mukkada VA, Rothenberg ME. J Allergy Clin Immunol. 2019 May;143(5):1928-1930.e3. doi: 10.1016/j.jaci.2018.12.1002. Epub 2019 Jan 14.

Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis. Lyles J, Rothenberg M. Curr Opin Immunol. 2019 Oct;60:46-53. doi: 10.1016/j.coi.2019.04.004. Epub 2019 May 25.

Screening children for eosinophilic esophagitis: allergic and other risk factors. Ruffner MA, Capucilli P, Hill DA, Spergel JM. Expert Rev Clin Immunol. 2019 Apr;15(4):315-318. doi: 10.1080/1744666X.2019.1579643. Epub 2019 Feb 20.

The Salivary Microbiome Is Altered in Children With Eosinophilic Esophagitis and Correlates With Disease Activity. Hiremath G, Shilts MH, Boone HH, Correa H, Acra S, Tovchigrechko A, Rajagopala SV, Das SR. Clin Transl Gastroenterol. 2019 Jun;10(6):e00039. doi: 10.14309/ctg.0000000000000039.

Toll-like receptor 2 stimulation augments esophageal barrier integrity. Ruffner MA, Song L, Maurer K, Shi L, Carroll MC, Wang JX, Muir AB, Spergel JM, Sullivan KE. Allergy. 2019 Dec;74(12):2449-2460. doi: 10.1111/all.13968. Epub 2019 Jul 25.

Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus. Bailey DD, Zhang Y, van Soldt BJ, Jiang M, Suresh S, Nakagawa H, Rustgi AK, Aceves SS, Cardoso WV, Que J. Development. 2019 Dec 4;146(23):dev178855. doi: 10.1242/dev.178855.

A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia. Godwin B, Liacouras C, Mehta V, Eisenberg J, Agawu A, Brown-Whitehorn T, Ruffner MA, Verma R, Cianferoni A, Spergel JM, Muir AB. Front Pediatr. 2018 Jun 20;6:173. doi: 10.3389/fped.2018.00173. eCollection 2018.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites. Aceves SS, King E, Collins MH, Yang GY, Capocelli KE, Abonia JP, Atkins D, Bonis PA, Carpenter CL, Dellon ES, Eby MD, Falk GW, Gonsalves N, Gupta SK, Hirano I, Kocher K, Krischer JP, Leung J, Lipscomb J, Menard-Katcher P, Mukkada VA, Pan Z, Spergel JM, Sun Q, Wershil BK, Rothenberg ME, Furuta GT; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). J Allergy Clin Immunol. 2018 Jul;142(1):130-138.e1. doi: 10.1016/j.jaci.2018.05.014. Epub 2018 May 29.

Allergic components of eosinophilic esophagitis. Spergel J, Aceves SS. J Allergy Clin Immunol. 2018 Jul;142(1):1-8. doi: 10.1016/j.jaci.2018.05.001.

Assessing Adherence and Barriers to Long-Term Elimination Diet Therapy in Adults with Eosinophilic Esophagitis. Wang R, Hirano I, Doerfler B, Zalewski A, Gonsalves N, Taft T. Dig Dis Sci. 2018 Jul;63(7):1756-1762. doi: 10.1007/s10620-018-5045-0. Epub 2018 Apr 2.

Authors' response. Spergel JM, Dellon ES, Liacouras CA, Hirano I, Molina-Infante J, Bredenoord AJ, Furuta GT. Ann Allergy Asthma Immunol. 2018 Dec;121(6):747-748. doi: 10.1016/j.anai.2018.10.015. Epub 2018 Oct 13.

Biological therapies for eosinophilic gastrointestinal diseases. Wechsler JB, Hirano I. J Allergy Clin Immunol. 2018 Jul;142(1):24-31.e2. doi: 10.1016/j.jaci.2018.05.018. Epub 2018 May 31.

Clinical Implications of Pediatric Colonic Eosinophilia. Mark J, Fernando SD, Masterson JC, Pan Z, Capocelli KE, Furuta GT, de Zoeten EF. J Pediatr Gastroenterol Nutr. 2018 May;66(5):760-766. doi: 10.1097/MPG.0000000000001784.

Clinical tolerance in eosinophilic esophagitis. Ruffner MA, Brown-Whitehorn TF, Verma R, Cianferoni A, Gober L, Shuker M, Muir AB, Liacouras CA, Spergel JM. J Allergy Clin Immunol Pract. 2018 Mar-Apr;6(2):661-663. doi: 10.1016/j.jaip.2017.06.035. Epub 2017 Aug 12.

Commentary: Individuals affected by Eosinophilic Gastrointestinal Disorders Have Complex Unmet Needs and Experience Barriers to Care. Hiremath G, Dellon ES. J Rare Dis Res Treat. 2018;3(2):34-36. doi: 10.29245/2572-9411/2018/2.1155. Epub 2018 Jul 17.

Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis- Current Concepts and Perspectives for Steroid Use. Greuter T, Alexander JA, Straumann A, Katzka DA. Clin Transl Gastroenterol. 2018 Dec;9(12):e212. doi: 10.1038/s41424-018-0074-8.

Emerging drugs for eosinophilic esophagitis. Pesek RD, Gupta SK. Expert Opin Emerg Drugs. 2018 Jun;23(2):173-183. doi: 10.1080/14728214.2018.1483335. Epub 2018 Jun 8.

Environmental factors and eosinophilic esophagitis. Jensen ET, Dellon ES. J Allergy Clin Immunol. 2018 Jul;142(1):32-40. doi: 10.1016/j.jaci.2018.04.015. Epub 2018 May 2.

Eosinophilic Esophagitis. Wright BL, Spergel JM. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1799-1801. doi: 10.1016/j.jaip.2018.06.019.

Eosinophilic Esophagitis Is a Late Manifestation of the Allergic March. Hill DA, Grundmeier RW, Ramos M, Spergel JM. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1528-1533. doi: 10.1016/j.jaip.2018.05.010. Epub 2018 Jun 25.

Eosinophilic Esophagitis Reference Score Accurately Identifies Disease Activity and Treatment Effects in Children. Wechsler JB, Bolton SM, Amsden K, Wershil BK, Hirano I, Kagalwalla AF. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1056-1063. doi: 10.1016/j.cgh.2017.12.019. Epub 2017 Dec 15.

Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and Management. Steinbach EC, Hernandez M, Dellon ES. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1483-1495. doi: 10.1016/j.jaip.2018.06.012. Epub 2018 Jul 3.

Eosinophilic Esophagitis: an Important Comorbid Condition of Asthma?. Durrani SR, Mukkada VA, Guilbert TW. Clin Rev Allergy Immunol. 2018 Aug;55(1):56-64. doi: 10.1007/s12016-018-8670-7.

Eosinophilic Gastroenteritis and Colitis: Not Yet Ready for the Big Leagues. Zevit N, Furuta GT. J Pediatr Gastroenterol Nutr. 2018 Jul;67(1):1-2. doi: 10.1097/MPG.0000000000001998.

Eosinophilic Gastrointestinal Disorders Pathology. Collins MH, Capocelli K, Yang GY. Front Med (Lausanne). 2018 Jan 15;4:261. doi: 10.3389/fmed.2017.00261. eCollection 2017.

Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. Martin LJ, He H, Collins MH, Abonia JP, Biagini Myers JM, Eby M, Johansson H, Kottyan LC, Khurana Hershey GK, Rothenberg ME. J Allergy Clin Immunol. 2018 May;141(5):1690-1698. doi: 10.1016/j.jaci.2017.09.046. Epub 2017 Nov 10.

Eosinophilic esophagitis: Time to classify into endotypes?. Ferguson AE, Fulkerson PC. J Allergy Clin Immunol. 2018 Jul;142(1):71-72. doi: 10.1016/j.jaci.2018.04.025. Epub 2018 May 8.

Eosinophilic esophagitis: pathophysiology and its clinical implications. Inage E, Furuta GT, Menard-Katcher C, Masterson JC. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G879-G886. doi: 10.1152/ajpgi.00174.2018. Epub 2018 Sep 13.

Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study. Shoda T, Wen T, Aceves SS, Abonia JP, Atkins D, Bonis PA, Caldwell JM, Capocelli KE, Carpenter CL, Collins MH, Dellon ES, Eby MD, Gonsalves N, Gupta SK, Falk GW, Hirano I, Menard-Katcher P, Kuhl JT, Krischer JP, Leung J, Mukkada VA, Spergel JM, Trimarchi MP, Yang GY, Zimmermann N, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Lancet Gastroenterol Hepatol. 2018 Jul;3(7):477-488. doi: 10.1016/S2468-1253(18)30096-7. Epub 2018 May 3.

Epidemiology and Natural History of Eosinophilic Esophagitis. Dellon ES, Hirano I. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.

Epithelial acid imbalance in patients with eosinophilic esophagitis. Hill DA, Spergel JM. J Allergy Clin Immunol. 2018 Dec;142(6):1757-1758. doi: 10.1016/j.jaci.2018.09.026. Epub 2018 Oct 10.

Epithelial origin of eosinophilic esophagitis. Rochman M, Azouz NP, Rothenberg ME. J Allergy Clin Immunol. 2018 Jul;142(1):10-23. doi: 10.1016/j.jaci.2018.05.008.

Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine. Whelan KA, Muir AB, Nakagawa H. Cell Mol Gastroenterol Hepatol. 2018 Jan 31;5(4):461-478. doi: 10.1016/j.jcmgh.2018.01.011. eCollection 2018.

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis. Fahey LM, Chandramouleeswaran PM, Guan S, Benitez AJ, Furuta GT, Aceves SS, Wang ML, Liacouras CA, Muir AB, Sleiman PM, Hakonarson H, Spergel JM, Cianferoni A. Clin Transl Gastroenterol. 2018 Mar 6;9(3):139. doi: 10.1038/s41424-018-0003-x.

Histologic improvement after 6 weeks of dietary elimination for eosinophilic esophagitis may be insufficient to determine efficacy. Philpott H, Dellon E. Asia Pac Allergy. 2018 Apr 25;8(2):e20. doi: 10.5415/apallergy.2018.8.e20. eCollection 2018 Apr.

Increased GATA-3 and T-bet expression in eosinophilic esophagitis versus gastroesophageal reflux disease. Wright BL, Nguyen N, Shim KP, Masterson JC, Jacobsen EA, Ochkur SI, Lee JJ, Furuta GT. J Allergy Clin Immunol. 2018 May;141(5):1919-1921.e5. doi: 10.1016/j.jaci.2017.12.993. Epub 2018 Jan 31.

Individuals affected by eosinophilic gastrointestinal disorders have complex unmet needs and frequently experience unique barriers to care. Hiremath G, Kodroff E, Strobel MJ, Scott M, Book W, Reidy C, Kyle S, Mack D, Sable K, Abonia P, Spergel J, Gupta SK, Furuta TG, Rothenberg ME, Dellon ES. Clin Res Hepatol Gastroenterol. 2018 Oct;42(5):483-493. doi: 10.1016/j.clinre.2018.03.003. Epub 2018 Mar 31.

Is eosinophilic esophagitis a member of the atopic march?. Hill DA, Spergel JM. Ann Allergy Asthma Immunol. 2018 Feb;120(2):113-114. doi: 10.1016/j.anai.2017.10.003.

Latest Insights on the Relationship Between Symptoms and Biologic Findings in Adults with Eosinophilic Esophagitis. Safroneeva E, Straumann A, Schoepfer AM. Gastrointest Endosc Clin N Am. 2018 Jan;28(1):35-45. doi: 10.1016/j.giec.2017.08.001.

Management of Esophageal Food Impaction Varies Among Gastroenterologists and Affects Identification of Eosinophilic Esophagitis. Hiremath G, Vaezi MF, Gupta SK, Acra S, Dellon ES. Dig Dis Sci. 2018 Jun;63(6):1428-1437. doi: 10.1007/s10620-018-4972-0. Epub 2018 Feb 20.

New Developments in the Diagnosis, Therapy, and Monitoring of Eosinophilic Esophagitis. Patel RV, Hirano I. Curr Treat Options Gastroenterol. 2018 Mar;16(1):15-26. doi: 10.1007/s11938-018-0167-1.

New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting. Spergel JM, Aceves SS, Kliewer K, Gonsalves N, Chehade M, Wechsler JB, Groetch M, Friedlander J, Dellon ES, Book W, Hirano I, Muir AB, Cianferoni A, Spencer L, Liacouras CA, Cheng E, Kottyan L, Wen T, Platts-Mills T, Rothenberg ME. J Allergy Clin Immunol. 2018 Jul;142(1):48-53. doi: 10.1016/j.jaci.2018.05.005. Epub 2018 May 24.

Nonesophageal Eosinophilic Gastrointestinal Disorders: Clinical Care and Future Directions. Naramore S, Gupta SK. J Pediatr Gastroenterol Nutr. 2018 Sep;67(3):318-321. doi: 10.1097/MPG.0000000000002040.

Pathophysiology of Eosinophilic Esophagitis. O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.

Pediatric Eosinophilic Esophagitis Endotypes: Are We Closer to Predicting Treatment Response?. Ferguson AE, Mukkada VA, Fulkerson PC. Clin Rev Allergy Immunol. 2018 Aug;55(1):43-55. doi: 10.1007/s12016-017-8658-8.

Pediatric eosinophilic esophagitis: updates for the primary care setting. Ruffner MA, Spergel JM. Curr Opin Pediatr. 2018 Dec;30(6):829-836. doi: 10.1097/MOP.0000000000000698.

Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research. Chehade M, Jones SM, Pesek RD, Burks AW, Vickery BP, Wood RA, Leung DYM, Furuta GT, Fleischer DM, Henning AK, Dawson P, Lindblad RW, Sicherer SH, Abonia JP, Sherrill JD, Sampson HA, Rothenberg ME. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1534-1544.e5. doi: 10.1016/j.jaip.2018.05.038. Epub 2018 Aug 1.

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). Khoury P, Akuthota P, Ackerman SJ, Arron JR, Bochner BS, Collins MH, Kahn JE, Fulkerson PC, Gleich GJ, Gopal-Srivastava R, Jacobsen EA, Leiferman KM, Francesca LS, Mathur SK, Minnicozzi M, Prussin C, Rothenberg ME, Roufosse F, Sable K, Simon D, Simon HU, Spencer LA, Steinfeld J, Wardlaw AJ, Wechsler ME, Weller PF, Klion AD. J Leukoc Biol. 2018 Jul;104(1):69-83. doi: 10.1002/JLB.5MR0118-028R. Epub 2018 Apr 19.

Summary of the updated international consensus diagnostic criteria for eosinophilic esophagitis: AGREE conference. Spergel JM, Dellon ES, Liacouras CA, Hirano I, Molina-Infante J, Bredenoord AJ, Furuta GT; participants of AGREE. Ann Allergy Asthma Immunol. 2018 Sep;121(3):281-284. doi: 10.1016/j.anai.2018.05.035. Epub 2018 Jul 18.

TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis. Nguyen N, Fernando SD, Biette KA, Hammer JA, Capocelli KE, Kitzenberg DA, Glover LE, Colgan SP, Furuta GT, Masterson JC. Mucosal Immunol. 2018 Mar;11(2):415-426. doi: 10.1038/mi.2017.72. Epub 2017 Aug 23.

The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes. Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. Cell Mol Gastroenterol Hepatol. 2018 Jan 3;5(3):333-352. doi: 10.1016/j.jcmgh.2017.12.013. eCollection 2018 Mar.

The Occasional Ebb and Flow between Eosinophilic Esophagitis and IgE-Mediated Food Allergy. Atkins D. J Allergy Clin Immunol Pract. 2018 Mar-Apr;6(2):651-652. doi: 10.1016/j.jaip.2017.11.011.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses. Azouz NP, Ynga-Durand MA, Caldwell JM, Jain A, Rochman M, Fischesser DM, Ray LM, Bedard MC, Mingler MK, Forney C, Eilerman M, Kuhl JT, He H, Biagini Myers JM, Mukkada VA, Putnam PE, Khurana Hershey GK, Kottyan LC, Wen T, Martin LJ, Rothenberg ME. Sci Transl Med. 2018 Jun 6;10(444):eaap9736. doi: 10.1126/scitranslmed.aap9736.

The atopic march: Critical evidence and clinical relevance. Hill DA, Spergel JM. Ann Allergy Asthma Immunol. 2018 Feb;120(2):131-137. doi: 10.1016/j.anai.2017.10.037.

The role of maintenance therapy in eosinophilic esophagitis: who, why, and how?. Philpott H, Dellon ES. J Gastroenterol. 2018 Feb;53(2):165-171. doi: 10.1007/s00535-017-1397-z. Epub 2017 Oct 10.

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ. Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.

What Is the Relationship Between Eosinophilic Esophagitis (EoE) and Aeroallergens? Implications for Allergen Immunotherapy. Egan M, Atkins D. Curr Allergy Asthma Rep. 2018 Jun 16;18(8):43. doi: 10.1007/s11882-018-0798-2.

Aeroallergens in Eosinophilic Esophagitis: Significant Triggers or Noise in the System?. Atkins D. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):1-2. doi: 10.1097/MPG.0000000000001268.

Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Whelan KA, Merves JF, Giroux V, Tanaka K, Guo A, Chandramouleeswaran PM, Benitez AJ, Dods K, Que J, Masterson JC, Fernando SD, Godwin BC, Klein-Szanto AJ, Chikwava K, Ruchelli ED, Hamilton KE, Muir AB, Wang ML, Furuta GT, Falk GW, Spergel JM, Nakagawa H. Gut. 2017 Jul;66(7):1197-1207. doi: 10.1136/gutjnl-2015-310341. Epub 2016 Feb 16.

Clarifying misunderstandings and misinterpretations about proton pump inhibitor-responsive oesophageal eosinophilia. Molina-Infante J, Hirano I, Spechler SJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Gut. 2017 Jun;66(6):1173-1174. doi: 10.1136/gutjnl-2016-312851. Epub 2016 Sep 13.

Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel. Wen T, Rothenberg ME. Front Med (Lausanne). 2017 Jul 14;4:108. doi: 10.3389/fmed.2017.00108. eCollection 2017.

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Cheng K, Gupta SK, Kantor S, Kuhl JT, Aceves SS, Bonis PA, Capocelli KE, Carpenter C, Chehade M, Collins MH, Dellon ES, Falk GW, Gopal-Srivastava R, Gonsalves N, Hirano I, King EC, Leung J, Krischer JP, Mukkada VA, Schoepfer A, Spergel JM, Straumann A, Yang GY, Furuta GT, Rothenberg ME. Transl Sci Rare Dis. 2017 Dec 18;2(3-4):141-155. doi: 10.3233/TRD-170016.

Diet and Stress in Pediatric Eosinophilic Esophagitis. Case C, Furuta GT, Atkins D, Pan Z, Robinson J. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):281-284. doi: 10.1097/MPG.0000000000001481.

Dilation of Pediatric Eosinophilic Esophagitis: Adverse Events and Short-term Outcomes. Menard-Katcher C, Furuta GT, Kramer RE. J Pediatr Gastroenterol Nutr. 2017 May;64(5):701-706. doi: 10.1097/MPG.0000000000001336.

Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis. Pesek RD, Rettiganti M, O'Brien E, Beckwith S, Daniel C, Luo C, Scurlock AM, Chandler P, Levy RA, Perry TT, Kennedy JL, Chervinskiy S, Vonlanthen M, Casteel H, Fiedorek SC, Gibbons T, Jones SM. Ann Allergy Asthma Immunol. 2017 Aug;119(2):177-183. doi: 10.1016/j.anai.2017.06.006. Epub 2017 Jul 1.

Eosinophilic Esophagitis: A Primary Disease of the Esophageal Mucosa. Abonia JP, Spergel JM, Cianferoni A. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):951-955. doi: 10.1016/j.jaip.2017.02.004. Epub 2017 Mar 28.

Eosinophilic esophagitis phenotypes: Ready for prime time?. Atkins D, Furuta GT, Liacouras CA, Spergel JM. Pediatr Allergy Immunol. 2017 Jun;28(4):312-319. doi: 10.1111/pai.12715. Epub 2017 May 4.

Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a Pediatric Cohort. Menard-Katcher C, Benitez AJ, Pan Z, Ahmed FN, Wilkins BJ, Capocelli KE, Liacouras CA, Verma R, Spergel JM, Furuta GT, Muir AB. Am J Gastroenterol. 2017 Sep;112(9):1466-1473. doi: 10.1038/ajg.2017.131. Epub 2017 May 16.

Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis. Eluri S, Book WM, Kodroff E, Strobel MJ, Gebhart JH, Jones PD, Menard-Katcher P, Ferris ME, Dellon ES. J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):53-57. doi: 10.1097/MPG.0000000000001415.

Management of refractory eosinophilic oesophagitis. Dellon ES. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):479-490. doi: 10.1038/nrgastro.2017.56. Epub 2017 May 24.

Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, Pentiuk S, Putnam PE, Abonia JP, Mukkada VA, Franciosi JP, Rothenberg ME. Dis Esophagus. 2017 Feb 1;30(3):1-8. doi: 10.1111/dote.12470.

Novel immunologic mechanisms in eosinophilic esophagitis. Caldwell JM, Paul M, Rothenberg ME. Curr Opin Immunol. 2017 Oct;48:114-121. doi: 10.1016/j.coi.2017.08.006. Epub 2017 Sep 29.

Propofol Use in Pediatric Patients With Food Allergy and Eosinophilic Esophagitis. Mehta P, Sundaram SS, Furuta GT, Pan Z, Atkins D, Markowitz S. J Pediatr Gastroenterol Nutr. 2017 Apr;64(4):546-549. doi: 10.1097/MPG.0000000000001291.

Proton pump inhibitor-responsive oesophageal eosinophilia: too early to change clinical practice. Muir AB, Wang ML, Metz D, Falk G, Markowitz J, Spergel JM, Liacouras CA. Gut. 2017 May;66(5):979-980. doi: 10.1136/gutjnl-2016-312601. Epub 2016 Jul 26.

Sticky Steroids: In Search of an Approved Treatment for Eosinophilic Esophagitis. Nguyen N, Furuta GT, Menard-Katcher C. J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):172-173. doi: 10.1097/MPG.0000000000001326.

The National Biome Initiative: An allergy perspective. Furuta GT, Aceves SS. J Allergy Clin Immunol. 2017 Apr;139(4):1131-1134. doi: 10.1016/j.jaci.2017.02.008. Epub 2017 Feb 28.

The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy. Hill DA, Dudley JW, Spergel JM. J Allergy Clin Immunol Pract. 2017 Mar-Apr;5(2):369-375. doi: 10.1016/j.jaip.2016.11.020. Epub 2016 Dec 30.

Toward More Efficient Dietary Elimination Therapy for Eosinophilic Esophagitis: The Fantastic 4?. Eluri S, Dellon ES. Clin Gastroenterol Hepatol. 2017 Nov;15(11):1668-1670. doi: 10.1016/j.cgh.2017.07.022. Epub 2017 Jul 26.

White Paper AGA: Drug Development for Eosinophilic Esophagitis. Hirano I, Spechler S, Furuta G, Dellon ES. Clin Gastroenterol Hepatol. 2017 Aug;15(8):1173-1183. doi: 10.1016/j.cgh.2017.03.016. Epub 2017 Mar 22.

2015 David Y. Graham Lecture: The First Two Decades Of Eosinophilic Esophagitis-From Acid Reflux To Food Allergy. Hirano I. Am J Gastroenterol. 2016 Jun;111(6):770-6. doi: 10.1038/ajg.2016.136. Epub 2016 Apr 12.

Advances in the endoscopic evaluation of eosinophilic esophagitis. Kia L, Hirano I. Curr Opin Gastroenterol. 2016 Jul;32(4):325-31. doi: 10.1097/MOG.0000000000000278.

Deeper Than the Epithelium: Role of Matrix and Fibroblasts in Pediatric and Adult Eosinophilic Esophagitis. Nguyen N, Furuta GT, Masterson JC. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):168-9. doi: 10.1097/MPG.0000000000001183.

Diets for diagnosis and management of food allergy: The role of the dietitian in eosinophilic esophagitis in adults and children. Venter C, Fleischer DM. Ann Allergy Asthma Immunol. 2016 Nov;117(5):468-471. doi: 10.1016/j.anai.2016.08.003. Epub 2016 Aug 31.

Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis. Morris DW, Stucke EM, Martin LJ, Abonia JP, Mukkada VA, Putnam PE, Rothenberg ME, Fulkerson PC. J Allergy Clin Immunol. 2016 Sep;138(3):915-918.e5. doi: 10.1016/j.jaci.2016.03.027. Epub 2016 May 16.

Eosinophilic Esophagitis-Associated Chemical and Mechanical Microenvironment Shapes Esophageal Fibroblast Behavior. Muir AB, Dods K, Henry SJ, Benitez AJ, Lee D, Whelan KA, DeMarshall M, Hammer DA, Falk G, Wells RG, Spergel J, Nakagawa H, Wang ML. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):200-9. doi: 10.1097/MPG.0000000000001100.

Eosinophilic Gastrointestinal Disorders Affect More Than Just the Esophagus. Gonsalves N, Furuta GT, Atkins D. J Pediatr Gastroenterol Nutr. 2016 Jan;62(1):1-2. doi: 10.1097/MPG.0000000000000993.

Eosinophilic esophagitis: search for noninvasive techniques for long-term monitoring. Watts A, Alexander JA, Gupta SK. Gastrointest Endosc. 2016 Feb;83(2):307-8. doi: 10.1016/j.gie.2015.07.006.

Eosinophils, probiotics, and the microbiome. Rosenberg HF, Masterson JC, Furuta GT. J Leukoc Biol. 2016 Nov;100(5):881-888. doi: 10.1189/jlb.3RI0416-202R. Epub 2016 Aug 22.

Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30.

Mechanisms of Disease of Eosinophilic Esophagitis. Davis BP, Rothenberg ME. Annu Rev Pathol. 2016 May 23;11:365-93. doi: 10.1146/annurev-pathol-012615-044241. Epub 2016 Feb 24.

Microbiome and its impact on gastrointestinal atopy. Muir AB, Benitez AJ, Dods K, Spergel JM, Fillon SA. Allergy. 2016 Sep;71(9):1256-63. doi: 10.1111/all.12943. Epub 2016 Jun 23.

Narrow-caliber esophagus of eosinophilic esophagitis: difficult to define, resistant to remedy. Carlson DA, Hirano I. Gastrointest Endosc. 2016 Jun;83(6):1149-50. doi: 10.1016/j.gie.2016.01.034.

Non-IgE-mediated food allergy syndromes. Ruffner MA, Spergel JM. Ann Allergy Asthma Immunol. 2016 Nov;117(5):452-454. doi: 10.1016/j.anai.2016.04.014. Epub 2016 Oct 24.

Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE). Chandramouleeswaran PM, Shen D, Lee AJ, Benitez A, Dods K, Gambanga F, Wilkins BJ, Merves J, Noah Y, Toltzis S, Yearley JH, Spergel JM, Nakagawa H, Malefyt Rd, Muir AB, Wang ML. PLoS One. 2016 Mar 18;11(3):e0150968. doi: 10.1371/journal.pone.0150968. eCollection 2016.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Straumann A, Lucendo AJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Gut. 2016 Mar;65(3):524-31. doi: 10.1136/gutjnl-2015-310991. Epub 2015 Dec 18.

Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Cavagnero K, Miyanohara A, Dohil R, Kurten RC, Aceves SS. J Allergy Clin Immunol. 2016 Apr;137(4):1270-1272.e1. doi: 10.1016/j.jaci.2015.09.020. Epub 2015 Nov 2.

Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?. Kliewer KL, Venter C, Cassin AM, Abonia JP, Aceves SS, Bonis PA, Dellon ES, Falk GW, Furuta GT, Gonsalves N, Gupta SK, Hirano I, Kagalwalla A, Leung J, Mukkada VA, Spergel JM, Rothenberg ME. J Allergy Clin Immunol. 2016 Apr;137(4):1011-1014. doi: 10.1016/j.jaci.2015.10.040. Epub 2015 Dec 24.

Substantial Variability in Biopsy Practice Patterns Among Gastroenterologists for Suspected Eosinophilic Gastrointestinal Disorders. Dellon ES, Collins MH, Bonis PA, Leung J, Capocelli KE, Dohil R, Falk GW, Furuta GT, Menard-Katcher C, Gupta SK, Hirano I, Hiremath GS, Kagalwalla AF, Wershil BK, Liacouras CA, Muir AB, Mukkada VA, Putnam PE, Schoepfer AM, Straumann A, Wo JM, Yang GY, Rothenberg ME, Gonsalves N. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1842-1844. doi: 10.1016/j.cgh.2016.04.025. Epub 2016 Apr 22.

TGF-β1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. Rawson R, Yang T, Newbury RO, Aquino M, Doshi A, Bell B, Broide DH, Dohil R, Kurten R, Aceves SS. J Allergy Clin Immunol. 2016 Sep;138(3):791-800.e4. doi: 10.1016/j.jaci.2016.02.028. Epub 2016 Apr 8.

The Immunologic Mechanisms of Eosinophilic Esophagitis. Hill DA, Spergel JM. Curr Allergy Asthma Rep. 2016 Feb;16(2):9. doi: 10.1007/s11882-015-0592-3.

The Regulatory Function of Eosinophils. Wen T, Rothenberg ME. Microbiol Spectr. 2016 Oct;4(5):10.1128/microbiolspec.MCHD-0020-2015. doi: 10.1128/microbiolspec.MCHD-0020-2015.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Topical glucocorticoid vs. diet therapy in eosinophilic esophagitis: the need for better treatment options. Imam T, Gupta SK. Expert Rev Clin Immunol. 2016 Aug;12(8):797-9. doi: 10.1080/1744666X.2016.1191947. Epub 2016 Jun 13.

Allergic mechanisms of Eosinophilic oesophagitis. Leung J, Beukema KR, Shen AH. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):709-720. doi: 10.1016/j.bpg.2015.09.012. Epub 2015 Sep 11.

An allergist's perspective to the evaluation of Eosinophilic Esophagitis. Spergel JM. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):771-781. doi: 10.1016/j.bpg.2015.06.011. Epub 2015 Jul 8.

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies. Kia L, Hirano I. Nat Rev Gastroenterol Hepatol. 2015 Jul;12(7):379-386. doi: 10.1038/nrgastro.2015.75. Epub 2015 May 19.

Environmental and infectious factors in eosinophilic esophagitis. Jensen ET, Dellon ES. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):721-729. doi: 10.1016/j.bpg.2015.06.008. Epub 2015 Jul 17.

Eosinophilic Esophagitis. Furuta GT, Katzka DA. N Engl J Med. 2015 Oct 22;373(17):1640-8. doi: 10.1056/NEJMra1502863.

Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections. Mehta P, Furuta GT. Immunol Allergy Clin North Am. 2015 Aug;35(3):413-37. doi: 10.1016/j.iac.2015.04.003. Epub 2015 Jun 17.

From genetics to treatment of eosinophilic esophagitis. Cianferoni A, Spergel JM. Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):417-25. doi: 10.1097/ACI.0000000000000200.

Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, Wang ML. Microbiome. 2015 Jun 1;3:23. doi: 10.1186/s40168-015-0085-6. eCollection 2015.

Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches. Kochar B, Dellon ES. Expert Rev Gastroenterol Hepatol. 2015;9(11):1359-69. doi: 10.1586/17474124.2015.1088384. Epub 2015 Sep 12.

Molecular, genetic, and cellular bases for treating eosinophilic esophagitis. Rothenberg ME. Gastroenterology. 2015 May;148(6):1143-57. doi: 10.1053/j.gastro.2015.02.002. Epub 2015 Feb 7.

Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: more similarities than differences. Eluri S, Dellon ES. Curr Opin Gastroenterol. 2015 Jul;31(4):309-15. doi: 10.1097/MOG.0000000000000185.

Recent advances in the pathological understanding of eosinophilic esophagitis. Cianferoni A, Spergel JM, Muir A. Expert Rev Gastroenterol Hepatol. 2015;9(12):1501-10. doi: 10.1586/17474124.2015.1094372. Epub 2015 Oct 15.

Recognition and Assessment of Eosinophilic Esophagitis: The Development of New Clinical Outcome Metrics. Nguyen N, Furuta GT, Menard-Katcher C. Gastroenterol Hepatol (N Y). 2015 Oct;11(10):670-4.

The TGFβ1 Promoter SNP C-509T and Food Sensitization Promote Esophageal Remodeling in Pediatric Eosinophilic Esophagitis. Rawson R, Anilkumar A, Newbury RO, Bafna V, Aquino M, Palmquist J, Hoffman HM, Mueller JL, Dohil R, Broide DH, Aceves SS. PLoS One. 2015 Dec 14;10(12):e0144651. doi: 10.1371/journal.pone.0144651. eCollection 2015.

Therapeutic strategies in eosinophilic esophagitis: Induction, maintenance and refractory disease. Sodikoff J, Hirano I. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):829-839. doi: 10.1016/j.bpg.2015.09.002. Epub 2015 Sep 11.

Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study. Morgan FC, Yehia L, McDonald C, Martinez-Agosto JA, Hardan AY, Tamburro J, Sahin M, Bayart C, Eng C; Developmental Synaptopathies Consortium. J Am Acad Dermatol. 2023 Jul;89(1):90-98. doi: 10.1016/j.jaad.2022.01.045. Epub 2022 Feb 7.

Clinical Spectrum and Science Behind the Hamartomatous Polyposis Syndromes. Yehia L, Heald B, Eng C. Gastroenterology. 2023 Apr;164(5):800-811. doi: 10.1053/j.gastro.2023.01.026. Epub 2023 Jan 28.

Development and Feasibility of the Self-Report Quantified Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders Checklist (TAND-SQ). Heunis TM, Chambers N, Vanclooster S, Bissell S, Byars AW, Capal JK, Cukier S, Davis PE, de Vries MC, De Waele L, Flinn J, Gardner-Lubbe S, Gipson T, Kingswood JC, Krueger DA, Kumm AJ, Sahin M, Schoeters E, Smith C, Srivastava S, Takei M, van Eeghen AM, Waltereit R, Jansen AC, de Vries PJ. Pediatr Neurol. 2023 Oct;147:101-123. doi: 10.1016/j.pediatrneurol.2023.07.001. Epub 2023 Jul 7. PMID: 37598571

Tuberous sclerosis complex (TSC) is a genetic condition in which typically benign tumors affect multiple organs including the brain, kidneys, heart, lungs, eyes, and skin. TSC-associated neuropsychiatric disorders (TAND) include difficulties at the behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial levels. Although TAND are often present in individuals with TSC, they are also underidentified and undertreated.

In this study, researchers developed a self-report quantified TAND Checklist (TAND-SQ). The team conducted feasibility and acceptability testing of the TAND-SQ Checklist with 23 technical experts from the TAND consortium and 58 caregivers and individuals with TSC.

The resulting Checklist can be completed by caregivers or individuals with TSC and used to quantify TAND difficulties. Authors state that next steps include further validation of the checklist and development of a smartphone application.

Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study. Applequist J, Burroughs C, Merkel PA, Rothenberg M, Trapnell B, Desnick R, Sahin M, Krischer J. J Med Internet Res. 2023 Mar 14;25:e39262. doi: 10.2196/39262.

Epilepsy Severity Is Associated With Head Circumference and Growth Rate in Infants With Tuberous Sclerosis Complex. Levine A, Davis P, Zhang B, Peters J, Filip-Dhima R, Warfield SK, Prohl A, Capal J, Krueger D, Bebin EM, Northrup H, Wu JY, Sahin M; TACERN Study Group. Pediatr Neurol. 2023 Jul;144:26-32. doi: 10.1016/j.pediatrneurol.2023.03.015. Epub 2023 Mar 29.

In Context: A Developmental Model of Reward Processing, With Implications for Autism and Sensitive Periods. Clements CC, Ascunce K, Nelson CA. J Am Acad Child Adolesc Psychiatry. 2023 Nov;62(11):1200-1216. doi: 10.1016/j.jaac.2022.07.861. Epub 2022 Nov 3.

Longitudinal Analysis of Cancer Risk in Children and Adults With Germline PTEN Variants. Yehia L, Plitt G, Tushar AM, Joo J, Burke CA, Campbell SC, Heiden K, Jin J, Macaron C, Michener CM, Pederson HJ, Radhakrishnan K, Shin J, Tamburro J, Patil S, Eng C. JAMA Netw Open. 2023 Apr 3;6(4):e239705. doi: 10.1001/jamanetworkopen.2023.9705.

Longitudinal neurobehavioral profiles in children and young adults with PTEN hamartoma tumor syndrome and reliable methods for assessing neurobehavioral change. Busch RM, Frazier Ii TW, Sonneborn C, Hogue O, Klaas P, Srivastava S, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C. J Neurodev Disord. 2023 Jan 14;15(1):3. doi: 10.1186/s11689-022-09468-4. PMID: 36641436; PMCID: PMC9840250.

PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations in the PTEN gene, which typically suppresses formation of tumors. In addition to its role in cancer, PTEN plays crucial roles in brain function. Individuals with PHTS show distinct neurobehavioral profiles, suggesting primary disruption of frontal lobe systems. More severe cognitive deficits are seen in individuals with associated autism spectrum disorder (ASD) that also extend to other areas of neurobehavioral function, such as adaptive behavior and sensory deficits. In this study, researchers aimed to characterize longitudinal neurobehavioral profiles in individuals with PHTS. Ninety-two children and young adults with PHTS and/or ASD completed two to three neurobehavioral evaluations over a two-year time period. The team used spaghetti plots and linear mixed effects models to visualize individual patient profiles and group trends, examining differences in cognitive and behavioral test scores over time. Results suggest that neurobehavioral characteristics observed in individuals with PHTS remain relatively stable over time, even in those with ASD. Reliable change indices and standardized regression-based change scores were calculated and provided in an easy-to-use Excel calculator that can be used in future research to examine patient outcomes at the individual level and inform intervention strategies.

Morphological Features of Language Regions in Individuals with Tuberous Sclerosis Complex. Ahtam B, Yun HJ, Vyas R, Pienaar R, Wilson JH, Goswami CP, Berto LF, Warfield SK, Sahin M, Grant PE, Peters JM, Im K. J Autism Dev Disord. 2023 May 24. doi: 10.1007/s10803-023-06004-8. Online ahead of print.

Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis. Cohen AL, Kroeck MR, Wall J, McManus P, Ovchinnikova A, Sahin M, Krueger DA, Bebin EM, Northrup H, Wu JY, Warfield SK, Peters JM, Fox MD; Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group. Ann Neurol. 2023 Mar;93(3):577-590. doi: 10.1002/ana.26551. Epub 2022 Nov 30. PMID: 36394118; PMCID: PMC9974824.

Tuberous sclerosis complex (TSC) is a genetic condition in which typically benign tumors affect multiple organs. TSC is associated with tubers—tumors that form in the brain—and a high incidence of autism spectrum disorder (ASD).

In this study, researchers explored the relationship between location of brain tubers and ASD diagnosis. The team began by determining tuber locations for 115 TSC patients with and without ASD. Next, researchers tested for associations between ASD diagnosis and tuber burden within the whole brain and specific locations relevant to ASD. Finally, they created a map of the data to calculate the risk of ASD.  

Results show that tubers involving the right fusiform face area (FFA) were associated with a 3.7-fold increased risk of developing ASD. Authors note that this strong association highlights a potential causal mechanism for developing autism in TSC, which may help guide more general research on ASD symptoms.

Updated consensus guidelines on the management of Phelan-McDermid syndrome. Srivastava S, Sahin M, Buxbaum JD, Berry-Kravis E, Soorya LV, Thurm A, Bernstein JA, Asante-Otoo A, Bennett WE Jr, Betancur C, Brickhouse TH, Passos Bueno MR, Chopra M, Christensen CK, Cully JL, Dies K, Friedman K, Gummere B, Holder JL Jr, Jimenez-Gomez A, Kerins CA, Khan O, Kohlenberg T, Lacro RV, Levi LA, Levy T, Linnehan D, Eva L, Moshiree B, Neumeyer A, Paul SM, Phelan K, Persico A, Rapaport R, Rogers C, Saland J, Sethuram S, Shapiro J, Tarr PI, White KM, Wickstrom J, Williams KM, Winrow D, Wishart B, Kolevzon A. Am J Med Genet A. 2023 Jul 1. doi: 10.1002/ajmg.a.63312. Epub ahead of print. PMID: 37392087

Phelan–McDermid syndrome (PMS) is a genetic condition caused by the deletion of a small portion of chromosome 22 or a mutation in the SHANK3 gene resulting in a wide range of neurodevelopmental and systemic characteristics. The first guidelines for assessment and monitoring in individuals with PMS were published in 2014. Due to recent studies and investigations, knowledge about PMS has since grown significantly.

In this study, researchers aimed to update clinical management guidelines for PMS based on the latest knowledge. A taskforce of clinical experts in PMS and representatives from the parent community collaborated to produce specialty-specific guidelines—including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry.

These updated guidelines allow for improved assessment and monitoring of individuals with PMS. Authors highlight several areas for future research with plans to update the guidelines as new knowledge becomes available.

A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Srivastava S, Jo B, Zhang B, Frazier T, Gallagher AS, Peck F, Levin AR, Mondal S, Li Z, Filip-Dhima R, Geisel G, Dies KA, Diplock A, Eng C, Hanna R, Sahin M, Hardan A; Developmental Synaptopathies Consortium. Hum Mol Genet. 2022 Oct 10;31(20):3393-3404. doi: 10.1093/hmg/ddac111. PMID: 35594551.

PTEN hamartoma tumor syndrome (PHTS) is a complex neurodevelopmental disorder characterized by overactivity of the mechanistic target of rapamycin (mTOR) pathway, which serves as a major regulator of growth. Limited data suggest that mTOR inhibitors may be therapeutic for patients with PHTS. However, no placebo-controlled studies have explored the effects of mTOR inhibition on cognition and behavior in PHTS patients with or without autism. In this study, researchers conducted a phase II, placebo-controlled trial to examine the safety and efficacy of everolimus, an mTOR inhibitor, in patients with PHTS. The team measured cognitive and behavioral outcomes in addition to biomarkers of electroencephalography (measurement of electrical activity in different parts of the brain). Results show that everolimus was well tolerated in individuals with PHTS. Electroencephalography supported engagement of the drug target in the brain, and some of the secondary (but not primary) outcome measures moved in the direction of improvement. Although this trial provides early evidence that everolimus is safe for use in patients with PHTS, authors note that further study is needed.

Distinct metabolic profiles associated with autism spectrum disorder versus cancer in individuals with germline PTEN mutations. Yehia L, Ni Y, Sadler T, Frazier TW, Eng C.. NPJ Genom Med. 2022 Mar 3;7(1):16. doi: 10.1038/s41525-022-00289-x. PMID: 35241692; PMCID: PMC8894426.

Large 22q13.3 deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome. Breen MS, Fan X, Levy T, Pollak RM, Collins B, Osman A, Tocheva AS, Sahin M, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Kolevzon A, Buxbaum JD; Developmental Synaptopathies Consortium. HGG Adv. 2022 Sep 26;4(1):100145. doi: 10.1016/j.xhgg.2022.100145. eCollection 2023 Jan 12.

Strong evidence for genotype-phenotype correlations in Phelan-McDermid syndrome: results from the developmental synaptopathies consortium. Levy T, Foss-Feig JH, Betancur C, Siper PM, Trelles-Thorne MDP, Halpern D, Frank Y, Lozano R, Layton C, Britvan B, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Srivastava S, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Hum Mol Genet. 2022 Feb 21;31(4):625-637. doi: 10.1093/hmg/ddab280. PMID: 34559195; PMCID: PMC8863417.

Visual Evoked Potential Abnormalities in Phelan-McDermid Syndrome. Siper PM, Rowe MA, Guillory SB, Rouhandeh AA, George-Jones JL, Tavassoli T, Lurie S, Zweifach J, Weissman J, Foss-Feig J, Halpern D, Trelles MP, Mulhern MS, Brittenham C, Gordon J, Zemon V, Buxbaum JD, Kolevzon A. J Am Acad Child Adolesc Psychiatry. 2022 Apr;61(4):565-574.e1. doi: 10.1016/j.jaac.2021.07.006. Epub 2021 Jul 22. PMID: 34303785; PMCID: PMC8782912.

A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations. Hardan AY, Jo B, Frazier TW, Klaas P, Busch RM, Dies KA, Filip-Dhima R, Snow AV, Eng C, Hanna R, Zhang B, Sahin M. Contemp Clin Trials Commun. 2021 Feb 6;21:100733. doi: 10.1016/j.conctc.2021.100733. eCollection 2021 Mar.

Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders. Anderson NC, Chen PF, Meganathan K, Afshar Saber W, Petersen AJ, Bhattacharyya A, Kroll KL, Sahin M; Cross-IDDRC Human Stem Cell Working Group. Stem Cell Reports. 2021 Jun 8;16(6):1446-1457. doi: 10.1016/j.stemcr.2021.03.025. Epub 2021 Apr 15. PMID: 33861989; PMCID: PMC8190574.

Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations. Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. J Autism Dev Disord. 2021 Feb 17. doi: 10.1007/s10803-021-04881-5. Online ahead of print.

Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Frazier TW, Jaini R, Busch RM, Wolf M, Sadler T, Klaas P, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Mol Autism. 2021 Jan 28;12(1):5. doi: 10.1186/s13229-020-00406-6.

Although PTEN is a well-established risk gene for autism spectrum disorder (ASD), little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). In this study, researchers evaluated the influence of PTEN mutation and ASD diagnostic status on relevant pathway protein levels in peripheral blood. They also examined the associations between protein levels and neurobehavioral functions. They found that several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. These results show that protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. The team notes that future longitudinal analyses are needed to replicate these findings and evaluate relationships between protein and neurobehavioral measures.

Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex. Ihnen SKZ, Capal JK, Horn PS, Griffith M, Sahin M, Bebin EM, Wu JY, Northrup H, Krueger DA; TACERN study group. Pediatr Neurol. 2021 Oct;123:1-9. doi: 10.1016/j.pediatrneurol.2021.06.012. Epub 2021 Jul 6.

Tuberous sclerosis complex (TSC) is a multi-system genetic disease that causes benign tumors to grow in vital organs including the brain, kidneys, heart, eyes, lungs, and skin. Epilepsy in TSC typically presents with early onset, multiple seizure types, and intractability. However, this varies among individual patients. In this study, researchers aimed to define epilepsy profiles in the TSC population. The team prospectively collected detailed individual data on seizure characteristics in children aged zero to 36 months. Caregivers kept daily seizure diaries, including onset and daily counts, for each seizure type. Researchers then compared developmental outcomes at 36 months between subgroups. Epilepsy was seen in 79 percent of participants. Hierarchical clustering based on six metrics of seizure burden—age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches—revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Within each group, subpopulations showed clinically meaningful differences in seizure burden, and groups with higher burden had worse developmental outcomes at 36 months. These findings indicate that early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.

Harnessing rare variants in neuropsychiatric and neurodevelopment disorders-a Keystone Symposia report. Cable J, Purcell RH, Robinson E, Vorstman JAS, Chung WK, Constantino JN, Sanders SJ, Sahin M, Dolmetsch RE, Shah BM, Thurm A, Martin CL, Bearden CE, Mulle JG. Ann N Y Acad Sci. 2021 Dec;1506(1):5-17. doi: 10.1111/nyas.14658. Epub 2021 Aug 2. PMID: 34342000; PMCID: PMC8688183.

Neurodevelopmental neuropsychiatric disorders—such as autism spectrum disorder and schizophrenia—have strong genetic risk components, but researchers are still deciphering the underlying mechanisms. Rare variants could help us better understand the biological mechanisms for more common idiopathic diseases and reveal new therapeutic targets. This review summarizes insights from the 2021 Keystone eSymposium "Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants.” Experts describe progress in genomic discovery and human phenotyping, as well as raise consistent issues.

Interplay Between Class II HLA Genotypes and the Microbiome and Immune Phenotypes in Individuals With PTEN Hamartoma Tumor Syndrome. Jia M, Sangwan N, Tzeng A, Eng C.. JCO Precis Oncol. 2021 Feb 9;5:PO.20.00374. doi: 10.1200/PO.20.00374. PMID: 34250407; PMCID: PMC8232567.

Multivariate data analysis identifies natural clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND). de Vries PJ, Leclezio L, Gardner-Lubbe S, Krueger D, Sahin M, Sparagana S, De Waele L, Jansen A. Orphanet J Rare Dis. 2021 Oct 24;16(1):447. doi: 10.1186/s13023-021-02076-w. PMID: 34689816; PMCID: PMC8543869.

Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome. Srivastava S, Condy E, Carmody E, Filip-Dhima R, Kapur K, Bernstein JA, Berry-Kravis E, Powell CM, Soorya L, Thurm A, Buxbaum JD, Sahin M, Kolevzon AL; Developmental Synaptopathies Consortium. J Neurodev Disord. 2021 Nov 5;13(1):53. doi: 10.1186/s11689-021-09398-7. PMID: 34740315; PMCID: PMC8570010.

Repetitive behaviors are often seen in individuals with autism spectrum disorder as well as intellectual disability. Due to the association of these diagnoses with Phelan-McDermid syndrome (PMS), researchers characterized the severity and profile of repetitive behaviors in PMS relative to previously published scores in other neurodevelopmental disorders. The team used the Repetitive Behavior Scale-Revised (RBS-R) as a parent-report measure of what was collected as part of a natural history study of PMS through the Developmental Synaptopathies Consortium (DSC). Researchers demonstrated that individuals with PMS in this cohort had lower rates of repetitive behaviors compared to previous studies of individuals with autism spectrum disorder and Fragile X syndrome. They also showed that more severe motor repetitive behaviors (e.g., body rocking, finger movements) were associated with lower IQ scores in PMS, but this relationship was not present between IQ and other types of repetitive behaviors. These findings indicate that repetitive behaviors may be milder overall in PMS compared to previous studies characterizing autism spectrum disorder and other genetic conditions. Stereotyped motor behaviors may be related to level of cognitive functioning, and not an autism spectrum disorder diagnosis, in PMS. Authors note the need to better understand these findings by continuing to study repetitive behaviors in PMS using objective measures.

Profile of Autism Spectrum Disorder in Tuberous Sclerosis Complex: Results from a Longitudinal, Prospective, Multisite Study. Capal JK, Williams ME, Pearson DA, Kissinger R, Horn PS, Murray D, Currans K, Kent B, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA; TACERN Study Group. Ann Neurol. 2021 Dec;90(6):874-886. doi: 10.1002/ana.26249. Epub 2021 Oct 29. PMID: 34668231; PMCID: PMC8639652.

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that causes noncancerous tumors to develop in many parts of the body. It is highly associated with autism spectrum disorder (ASD). Researchers seeking to characterize autistic features in young children with TSC evaluated 138 children from ages 3 to 36 months. They used both development and autism-specific assessments. One in four children in the study had been diagnosed with ASD by 36 months. Many individuals with TSC without an autism diagnosis also exhibited a range of autistic behaviors that were below the diagnostic threshold. Study authors report a broader autism phenotype (set of characteristics) that can be identified in young children with TSC, offering an opportunity for early, targeted treatments.

Psychiatric Characteristics Across Individuals With PTEN Mutations. Steele M, Uljarević M, Rached G, Frazier TW, Phillips JM, Libove RA, Busch RM, Klaas P, Martinez-Agosto JA, Srivastava S, Eng C, Sahin M, Hardan AY. Front Psychiatry. 2021 Aug 17;12:672070. doi: 10.3389/fpsyt.2021.672070. eCollection 2021.

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome. Mariscal MG, Berry-Kravis E, Buxbaum JD, Ethridge LE, Filip-Dhima R, Foss-Feig JH, Kolevzon A, Modi ME, Mosconi MW, Nelson CA, Powell CM, Siper PM, Soorya L, Thaliath A, Thurm A, Zhang B, Sahin M, Levin AR; Developmental Synaptopathies Consortium. Mol Autism. 2021 Apr 28;12(1):29. doi: 10.1186/s13229-020-00411-9.

Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study. Guillory SB, Baskett VZ, Grosman HE, McLaughlin CS, Isenstein EL, Wilkinson E, Weissman J, Britvan B, Trelles MP, Halpern DB, Buxbaum JD, Siper PM, Wang AT, Kolevzon A, Foss-Feig JH. J Neurodev Disord. 2021 Dec 4;13(1):58. doi: 10.1186/s11689-021-09400-2. PMID: 34863106.

Phelan-McDermid Syndrome (PMS) is a rare genetic disorder characterized by intellectual disability and motor delays. It is also one of the most common genetic causes of autism spectrum disorder (ASD). Social deficits are a core feature of ASD. In order to characterize social attention and recognition memory, researchers tested a group of patients with PMS and another group of patients with idiopathic (no cause identified) ASD on a visual paired-comparison task. They analyzed the behavior of test subjects looking at a novel image versus a previously viewed, familiar image. Researchers found differences in attention and memory for social stimuli in the PMS group v. the idiopathic ASD group. Study authors say that these unique patterns could both clarify underlying mechanistic alterations and inform treatment targets for PMS. They could also help stratify individuals with idiopathic ASD and potentially apply knowledge gained in PMS to those individuals.

Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous PTEN mutations. Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. Am J Med Genet A. 2021 Aug 23. doi: 10.1002/ajmg.a.62458. Online ahead of print.

Mutations in the PTEN gene are an important genetic risk factor for autism spectrum disorder (ASD). PTEN mutations are identified in 2% of all ASD cases and 17-20% of cases with both ASD and macrocephaly (larger than typical head size). Restricted and repetitive behaviors (RRB) are a core diagnostic symptom of ASD and one of the earlier predictors of a subsequent ASD diagnosis. RRBs include repetitive motor behaviors (RMB), insistence on sameness (IS), and circumscribed interests (CI). Researchers believe these symptom domains, which have a significant negative impact on affected individuals and their families, likely have distinct mechanisms and might therefore require different treatments. Seeking to develop a more nuanced understanding of RRB in individuals with PTEN mutations, researchers compared RMB, IS, and CI symptoms captured by two different measures across three groups: 38 individuals with PTEN mutations with ASD, 23 with PTEN mutations without ASD, and 25 with ASD and macrocephaly but without PTEN mutations. After adjusting for age and full-scale intelligence quotient (FSIQ) scores, the researchers found that differences between the three study groups were not statistically significant. However, all three symptom domains showed distinct association patterns with sex, age, and FSIQ. Study authors conclude that their findings highlight the importance of comprehensively assessing RRB in people with PTEN mutations. Their findings further support the hypothesis that RMB, IS, and CI are indeed distinct RRB domains that might, therefore, require different treatment approaches in this population. They recommend that future studies are needed to further understand mechanisms behind specific RRB subdomains and inform most optimal strategies for individuation of treatment options. This research offers the largest, most comprehensive comparison of distinct RRB domains in individuals with PTEN mutations to date.

Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network. Cohen AL, Mulder BPF, Prohl AK, Soussand L, Davis P, Kroeck MR, McManus P, Gholipour A, Scherrer B, Bebin EM, Wu JY, Northrup H, Krueger DA, Sahin M, Warfield SK, Fox MD, Peters JM; Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group. Ann Neurol. 2021 Apr;89(4):726-739. doi: 10.1002/ana.26015. Epub 2021 Jan 21.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

Copy Number Variation and Clinical Outcomes in Patients With Germline PTEN Mutations. Yehia L, Seyfi M, Niestroj LM, Padmanabhan R, Ni Y, Frazier TW, Lal D, Eng C. JAMA Netw Open. 2020 Jan 3;3(1):e1920415. doi: 10.1001/jamanetworkopen.2019.20415.

Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome. Bassell J, Srivastava S, Prohl AK, Scherrer B, Kapur K, Filip-Dhima R, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Buxbaum JD, Kolevzon A, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Pediatr Neurol. 2020 May;106:24-31. doi: 10.1016/j.pediatrneurol.2020.01.006. Epub 2020 Jan 31.

Editorial: Biomarkers to Enable Therapeutics Development in Neurodevelopmental Disorders. Sahin M, Sweeney JA, Jones SR. Front Integr Neurosci. 2020 Nov 12;14:616641. doi: 10.3389/fnint.2020.616641. PMID: 33262695; PMCID: PMC7686575.

Epilepsy Risk Prediction Model for Patients With Tuberous Sclerosis Complex. Farach LS, Richard MA, Lupo PJ, Sahin M, Krueger DA, Wu JY, Bebin EM, Au KS, Northrup H; TACERN Study Group. Pediatr Neurol. 2020 Dec;113:46-50. doi: 10.1016/j.pediatrneurol.2020.07.015. Epub 2020 Jul 29.

LEARNING TO DETECT BRAIN LESIONS FROM NOISY ANNOTATIONS. Karimi D, Peters JM, Ouaalam A, Prabhu SP, Sahin M, Krueger DA, Kolevzon A, Eng C, Warfield SK, Gholipour A. Proc IEEE Int Symp Biomed Imaging. 2020 Apr;2020:1910-1914. doi: 10.1109/isbi45749.2020.9098599. Epub 2020 May 22.

Language predictors of autism spectrum disorder in young children with tuberous sclerosis complex. Schoenberger A, Capal JK, Ondracek A, Horn PS, Murray D, Byars AW, Pearson DA, Williams ME, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA. Epilepsy Behav. 2020 Feb;103(Pt A):106844. doi: 10.1016/j.yebeh.2019.106844. Epub 2019 Dec 18.

Lesion-Constrained Electrical Source Imaging: A Novel Approach in Epilepsy Surgery for Tuberous Sclerosis Complex. Peters JM, Hyde DE, Chu CJ, Boom M, Scherrer B, Madsen JR, Stone SS, Ouaalam H, Prabhu SP, Sahin M, Warfield SK. J Clin Neurophysiol. 2020 Jan;37(1):79-86. doi: 10.1097/WNP.0000000000000615.

PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation?. Yehia L, Eng C. Hum Mol Genet. 2020 Oct 20;29(R2):R150-R157. doi: 10.1093/hmg/ddaa127.

More than 400 hereditary cancer syndromes have been described to date and account for 5-10% of all cancers. PTEN hamartoma tumour syndrome (PHTS) is an umbrella term for subsets of four syndromes associated with germline (inherited) PTEN mutations. However, many patients with phenotypes similar to those in PHTS do not carry germline PTEN mutations. This paper reviews gene discovery efforts over the last decade to identify alterations in cancer-predisposing genes in order to facilitate gene-informed molecular diagnosis, cancer risk assessment, and gene-specific clinical management. Authors conclude that validating these discoveries is critical to bringing these patients specific gene-informed risk assessment and subsequent management.

Polymicrogyria is Associated With Pathogenic Variants in PTEN. Shao DD, Achkar CM, Lai A, Srivastava S, Doan RN, Rodan LH, Chen AY; Brain Development Study Group, Poduri A, Yang E, Walsh CA. Ann Neurol. 2020 Dec;88(6):1153-1164. doi: 10.1002/ana.25904. Epub 2020 Oct 8.

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome. Kohlenberg TM, Trelles MP, McLarney B, Betancur C, Thurm A, Kolevzon A. J Neurodev Disord. 2020 Feb 12;12(1):7. doi: 10.1186/s11689-020-9309-6.

Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome. Gergoudis K, Weinberg A, Templin J, Farmer C, Durkin A, Weissman J, Siper P, Foss-Feig J, Del Pilar Trelles M, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Autism Res. 2020 Aug;13(8):1383-1396. doi: 10.1002/aur.2299. Epub 2020 May 14.

Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms. Nariai H, Hussain SA, Bernardo D, Motoi H, Sonoda M, Kuroda N, Asano E, Nguyen JC, Elashoff D, Sankar R, Bragin A, Staba RJ, Wu JY. Clin Neurophysiol. 2020 Nov;131(11):2527-2536. doi: 10.1016/j.clinph.2020.08.013. Epub 2020 Sep 3.

The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex. Scherrer B, Prohl AK, Taquet M, Kapur K, Peters JM, Tomas-Fernandez X, Davis PE, M Bebin E, Krueger DA, Northrup H, Y Wu J, Sahin M, Warfield SK. Cereb Cortex. 2020 Apr 14;30(4):2199-2214. doi: 10.1093/cercor/bhz233.

A unified circuit for social behavior. Modi ME, Sahin M. Neurobiol Learn Mem. 2019 Nov;165:106920. doi: 10.1016/j.nlm.2018.08.010. Epub 2018 Aug 24.

Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer. Smith IN, Thacker S, Seyfi M, Cheng F, Eng C. Am J Hum Genet. 2019 May 2;104(5):861-878. doi: 10.1016/j.ajhg.2019.03.009. Epub 2019 Apr 18.

Distinct Alterations in Tricarboxylic Acid Cycle Metabolites Associate with Cancer and Autism Phenotypes in Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome. Yehia L, Ni Y, Feng F, Seyfi M, Sadler T, Frazier TW, Eng C. Am J Hum Genet. 2019 Oct 3;105(4):813-821. doi: 10.1016/j.ajhg.2019.09.004. Epub 2019 Sep 26.

Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes. Smith IN, Thacker S, Jaini R, Eng C. J Biomol Struct Dyn. 2019 Apr;37(7):1766-1782. doi: 10.1080/07391102.2018.1465854. Epub 2018 May 14.

Incontinence in Phelan-McDermid Syndrome. Witmer C, Mattingly A, DʼSouza P, Thurm A, Hadigan C. J Pediatr Gastroenterol Nutr. 2019 Aug;69(2):e39-e42. doi: 10.1097/MPG.0000000000002342.

Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex. Davis PE, Kapur K, Filip-Dhima R, Trowbridge SK, Little E, Wilson A, Leuchter A, Bebin EM, Krueger D, Northrup H, Wu JY, Sahin M, Peters JM; Tuberous Sclerosis Autism Centers of Excellence Research Network. Epilepsia. 2019 Aug;60(8):1721-1732. doi: 10.1111/epi.16284. Epub 2019 Jul 12.

Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex. Peters JM, Prohl A, Kapur K, Nath A, Scherrer B, Clancy S, Prabhu SP, Sahin M, Franz DN, Warfield SK, Krueger DA. Pediatr Neurol. 2019 Jan;90:24-30. doi: 10.1016/j.pediatrneurol.2018.10.005. Epub 2018 Oct 18.

Motion-robust diffusion compartment imaging using simultaneous multi-slice acquisition. Marami B, Scherrer B, Khan S, Afacan O, Prabhu SP, Sahin M, Warfield SK, Gholipour A. Magn Reson Med. 2019 May;81(5):3314-3329. doi: 10.1002/mrm.27613. Epub 2018 Nov 16.

Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN. Busch RM, Srivastava S, Hogue O, Frazier TW, Klaas P, Hardan A, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Transl Psychiatry. 2019 Oct 8;9(1):253. doi: 10.1038/s41398-019-0588-1.

Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature. Kolevzon A, Delaby E, Berry-Kravis E, Buxbaum JD, Betancur C. Mol Autism. 2019 Dec 24;10:50. doi: 10.1186/s13229-019-0291-3. eCollection 2019.

PTEN-opathies: from biological insights to evidence-based precision medicine. Yehia L, Ngeow J, Eng C. J Clin Invest. 2019 Feb 1;129(2):452-464. doi: 10.1172/JCI121277. Epub 2019 Jan 7.

The tumor suppressor phosphatase and tensin homolog (PTEN) classically counteracts the PI3K/AKT/mTOR signaling cascade. Germline pathogenic PTEN mutations cause PTEN hamartoma tumor syndrome (PHTS), featuring various benign and malignant tumors, as well as neurodevelopmental disorders such as autism spectrum disorder. Germline and somatic mosaic mutations in genes encoding components of the PI3K/AKT/mTOR pathway downstream of PTEN predispose to syndromes with partially overlapping clinical features, termed the "PTEN-opathies." Experimental models of PTEN pathway disruption uncover the molecular and cellular processes influencing clinical phenotypic manifestations. Such insights not only teach us about biological mechanisms in states of health and disease, but also enable more accurate gene-informed cancer risk assessment, medical management, and targeted therapeutics. Hence, the PTEN-opathies serve as a prototype for bedside to bench, and back to the bedside, practice of evidence-based precision medicine.

Prospective observational study: Fast ripple localization delineates the epileptogenic zone. Nariai H, Hussain SA, Bernardo D, Fallah A, Murata KK, Nguyen JC, Rajaraman RR, Rao LM, Matsumoto JH, Lerner JT, Salamon N, Elashoff D, Sankar R, Wu JY. Clin Neurophysiol. 2019 Nov;130(11):2144-2152. doi: 10.1016/j.clinph.2019.08.026. Epub 2019 Sep 17.

Resting-State fMRI Networks in Children with Tuberous Sclerosis Complex. Ahtam B, Dehaes M, Sliva DD, Peters JM, Krueger DA, Bebin EM, Northrup H, Wu JY, Warfield SK, Sahin M, Grant PE; TACERN Study Group. J Neuroimaging. 2019 Nov;29(6):750-759. doi: 10.1111/jon.12653. Epub 2019 Jul 14.

Tuberous Sclerosis Complex Genotypes and Developmental Phenotype. Farach LS, Pearson DA, Woodhouse JP, Schraw JM, Sahin M, Krueger DA, Wu JY, Bebin EM, Lupo PJ, Au KS, Northrup H; TACERN Study Group. Pediatr Neurol. 2019 Jul;96:58-63. doi: 10.1016/j.pediatrneurol.2019.03.003. Epub 2019 Mar 13.

Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome. Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Pediatr Neurol. 2019 Jan;90:37-43. doi: 10.1016/j.pediatrneurol.2018.09.008. Epub 2018 Sep 21.

White matter mean diffusivity correlates with myelination in tuberous sclerosis complex. Peters JM, Struyven RR, Prohl AK, Vasung L, Stajduhar A, Taquet M, Bushman JJ, Lidov H, Singh JM, Scherrer B, Madsen JR, Prabhu SP, Sahin M, Afacan O, Warfield SK. Ann Clin Transl Neurol. 2019 Jul;6(7):1178-1190. doi: 10.1002/acn3.793. Epub 2019 Jun 23.

A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). de Vries PJ, Wilde L, de Vries MC, Moavero R, Pearson DA, Curatolo P. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):309-320. doi: 10.1002/ajmg.c.31637. Epub 2018 Aug 16.

Assessing the validity of the approximation of diffusion-weighted-MRI signals from crossing fascicles by sums of signals from single fascicles. Rensonnet G, Scherrer B, Warfield SK, Macq B, Taquet M. Magn Reson Med. 2018 Apr;79(4):2332-2345. doi: 10.1002/mrm.26832. Epub 2017 Jul 16.

Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex. Baumer FM, Peters JM, Clancy S, Prohl AK, Prabhu SP, Scherrer B, Jansen FE, Braun KPJ, Sahin M, Stamm A, Warfield SK. Cereb Cortex. 2018 Oct 1;28(10):3665-3672. doi: 10.1093/cercor/bhx247.

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Mol Autism. 2018 Apr 27;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018.

Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels. Frazier TW, Klingemier EW, Parikh S, Speer L, Strauss MS, Eng C, Hardan AY, Youngstrom EA. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):858-866. doi: 10.1016/j.jaac.2018.06.023. Epub 2018 Sep 13.

Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder. Curtin P, Austin C, Curtin A, Gennings C, Arora M; (for the Emergent Dynamical Systems Group), Tammimies K, Willfors C, Berggren S, Siper P, Rai D, Meyering K, Kolevzon A, Mollon J, David AS, Lewis G, Zammit S, Heilbrun L, Palmer RF, Wright RO, Bölte S, Reichenberg A. Sci Adv. 2018 May 30;4(5):eaat1293. doi: 10.1126/sciadv.aat1293. eCollection 2018 May.

Framework for assessing individuals with rare genetic disorders associated with profound intellectual and multiple disabilities (PIMD): the example of Phelan McDermid Syndrome. Soorya L, Leon J, Trelles MP, Thurm A. Clin Neuropsychol. 2018 Aug-Oct;32(7):1226-1255. doi: 10.1080/13854046.2017.1413211. Epub 2017 Dec 21.

Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Peron A, Au KS, Northrup H. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):281-290. doi: 10.1002/ajmg.c.31651. Epub 2018 Sep 26.

High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex. Hussain SA, Schmid E, Peters JM, Goyal M, Bebin EM, Northrup H, Sahin M, Krueger DA, Wu JY; Tuberous Sclerosis Complex Autism Center of Excellence Network. Epilepsy Res. 2018 Dec;148:1-7. doi: 10.1016/j.eplepsyres.2018.09.016. Epub 2018 Oct 2.

Interrater reliability in visual identification of interictal high-frequency oscillations on electrocorticography and scalp EEG. Nariai H, Wu JY, Bernardo D, Fallah A, Sankar R, Hussain SA. Epilepsia Open. 2018 Nov 2;3(Suppl Suppl 2):127-132. doi: 10.1002/epi4.12266. eCollection 2018 Dec.

Prospective longitudinal overnight video-EEG evaluation in Phelan-McDermid Syndrome. Khan OI, Zhou X, Leon J, Kessler R, Gaughan T, D'Souza P, Gropman A, Cohen N, Rennert O, Buckley A, Inati S, Thurm A. Epilepsy Behav. 2018 Mar;80:312-320. doi: 10.1016/j.yebeh.2017.11.034. Epub 2018 Feb 3.

Removing high-frequency oscillations: A prospective multicenter study on seizure outcome.. Jacobs J, Wu JY, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, Gotman J. Neurology. 2018 Sep 11;91(11):e1040-e1052. doi: 10.1212/WNL.0000000000006158. Epub 2018 Aug 17. PMID: 30120133; PMCID:PMC6140372

The Way Forward for Mechanism-Based Therapeutics in Genetically Defined Neurodevelopmental Disorders. Modi ME, Sahin M. Clin Pharmacol Ther. 2018 Oct;104(4):603-606. doi: 10.1002/cpt.1181. Epub 2018 Aug 12.

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome. Farach LS, Little ME, Duker AL, Logan CV, Jackson A, Hecht JT, Bober M. Am J Med Genet A. 2018 Feb;176(2):465-469. doi: 10.1002/ajmg.a.38581. Epub 2017 Dec 19.

The microbiome in PTEN hamartoma tumor syndrome. Byrd V, Getz T, Padmanabhan R, Arora H, Eng C. Endocr Relat Cancer. 2017. PMID: 29233840.

Tuberous sclerosis complex. Peron A, Northrup H. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):274-277. doi: 10.1002/ajmg.c.31657. Epub 2018 Oct 16.

Vigabatrin for Epileptic Spasms and Tonic Seizures in Tuberous Sclerosis Complex. van der Poest Clement EA, Sahin M, Peters JM. J Child Neurol. 2018 Jul;33(8):519-524. doi: 10.1177/0883073818768309. Epub 2018 Apr 24.

Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex. Bernardo D, Nariai H, Hussain SA, Sankar R, Salamon N, Krueger DA, Sahin M, Northrup H, Bebin EM, Wu JY; UCLA Pediatric Epilepsy Group; TACERN Study Group. Clin Neurophysiol. 2018 Jul;129(7):1458-1466. doi: 10.1016/j.clinph.2018.03.010. Epub 2018 Apr 3.

A Meta-Analysis of Gaze Differences to Social and Nonsocial Information Between Individuals With and Without Autism. Frazier TW, Strauss M, Klingemier EW, Zetzer EE, Hardan AY, Eng C, Youngstrom EA. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):546-555. doi: 10.1016/j.jaac.2017.05.005. Epub 2017 May 11.

A clinician-administered observation and corresponding caregiver interview capturing DSM-5 sensory reactivity symptoms in children with ASD. Siper PM, Kolevzon A, Wang AT, Buxbaum JD, Tavassoli T. Autism Res. 2017 Jun;10(6):1133-1140. doi: 10.1002/aur.1750. Epub 2017 Mar 11.

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. Srivastava S, Sahin M. Srivastava S, Sahin M. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord. 2017;9:23. PMID: 28649286, PMCID: PMC5481888.

Influence of seizures on early development in tuberous sclerosis complex. Capal JK, Bernardino-Cuesta B, Horn PS, et al. Epilepsy Behav. 2017;70(Pt A):245-252. PMID: 28457992, PMCID: PMC5497719.

Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena. Hussain SA, Mathern GW, Hung P, Weng J, Sankar R, Wu JY. Epilepsy Res. 2017;135:79-86. PMID: 28644979, PMCID: PMC5568451.

Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder. Rankine J, Li E, Lurie S, Rieger H, Fourie E, Siper PM, Wang AT, Buxbaum JD, Kolevzon A. J Autism Dev Disord. 2017 Jun;47(6):1605-1617. doi: 10.1007/s10803-017-3082-8.

Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants. Davis PE, Filip-Dhima R, Sideridis G, Peters JM, Au KS, Northrup H, Bebin EM, Wu JY, Krueger D, Sahin M; Tuberous Sclerosis Complex Autism Center of Excellence Research Network. Pediatrics. 2017;140(6). PMID: 29101226, PMCID: PMC5703775.

The genomic landscape of tuberous sclerosis complex. Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE, Sisson KA, Koeman J, Weisenberger DJ, Cottingham SL, DeRoos ST, Devinsky O, Winn ME, Cherniack AD, Shen H, Northrup H, Krueger DA, MacKeigan JP. Nat Commun. 2017 Jun 15;8:15816. doi: 10.1038/ncomms15816.

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex. Capal JK, Horn PS, Murray DS, Byars AW, Bing NM, Kent B, Bucher LA, Williams ME, O'Kelley S, Pearson DA, Sahin M, Krueger DA; TACERN Study Group. Pediatr Neurol. 2017;75:80-86. PMID: 28844798, PMCID: PMC5610103.

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference. Sahin M, Henske EP, Manning BD, Ess KC, Bissler JJ, Klann E, Kwiatkowski DJ, Roberds SL, Silva AJ, Hillaire-Clarke CS, Young LR, Zervas M, Mamounas LA; Tuberous Sclerosis Complex Working Group to Update the Research Plan. Pediatr Neurol. 2016;60:1-12. PMID: 27267556, PMCID: PMC4921275.

Altered Structural Brain Networks in Tuberous Sclerosis Complex. Im K, Ahtam B, Haehn D, Peters JM, Warfield SK, Sahin M, Ellen Grant P. Cereb Cortex. 2016;26(5):2046-2058. PMID: 25750257, PMCID: PMC4830286.

Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND). Scherrer B, Schwartzman A, Taquet M, Sahin M, Prabhu SP, Warfield SK. Magn Reson Med. Sep 12 2015. PMID: 26362832.

Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism. Ebrahimi-Fakhari D, Saffari A, Wahlster L, Lu J, Byrne S, Hoffmann GF, Jungbluth H, Sahin M. Brain. 2016;139(Pt 2):317-337. PMID: 26715604.

Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders. Markowitz LA, Reyes C, Embacher RA, Speer LL, Roizen N, Frazier TW. Autism. 2016 Oct;20(7):832-44. doi: 10.1177/1362361315611382. Epub 2015 Dec 10.

Development of an Objective Autism Risk Index Using Remote Eye Tracking. Frazier TW, Klingemier EW, Beukemann M, Speer L, Markowitz L, Parikh S, Wexberg S, Giuliano K, Schulte E, Delahunty C, Ahuja V, Eng C, Manos MJ, Hardan AY, Youngstrom EA, Strauss MS. J Am Acad Child Adolesc Psychiatry. Apr 2016;55(4):301-309. PMID: 27015721, PMCID: PMC4808563.

Editorial: Essential Pathways and Circuits of Autism Pathogenesis. Dölen G, Sahin M. Front Neurosci. 2016 Apr 26;10:182. doi: 10.3389/fnins.2016.00182. eCollection 2016.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis. Krueger DA, Wilfong AA, Mays M, Talley CM, Agricola K, Tudor C, Capal J, Holland-Bouley K, Franz DN. Neurology. 2016 Dec 6;87(23):2408-2415. doi: 10.1212/WNL.0000000000003400. Epub 2016 Nov 4. PMID: 27815402; PMCID: PMC5177677.

Motion-Robust Diffusion-Weighted Brain MRI Reconstruction Through Slice-Level Registration-Based Motion Tracking. Marami B, Scherrer B, Afacan O, Erem B, Warfield SK, Gholipour A. IEEE Trans Med Imaging. 2016;35(10):2258-2269. PMID: 27834639, PMCID: PMC5108524.

Siper PM. Siper PM, Zemon V, Gordon J, et al. PLoS ONE. 2016;11(10):e0164422. PMID: 27716799, PMCID: PMC5055293.

Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Keppler-Noreuil KM, Parker VE, Darling TN, Martinez-Agosto JA. Am J Med Genet C Semin Med Genet. 2016;172(4):402-421. PMID: 27860216, PMCID: PMC5592089.

The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis. Key negative regulators of the PI3K-AKT signaling pathway include PTEN and TSC1/TSC2 and germline loss-of function mutations of these genes are established to cause PTEN Hamartoma Tumor Syndrome and Tuberous Sclerosis Complex. Mosaic forms of these conditions lead to increased activation of PI3K and mTOR at affected sites and there is phenotypic overlap between these conditions. All are associated with significant morbidity with limited options for treatment other than symptomatic therapies and surgeries. As dysregulation of the PI3K/AKT/mTOR pathway has been implicated in cancer, several small molecule inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are under clinical investigation. The development of these therapies brings closer the prospect of targeting treatment for somatic PI3K/AKT/mTOR-related overgrowth syndromes. This review describes the clinical findings, gene function and pathogenesis of these mosaic overgrowth syndromes, and presents existing and future treatment strategies to reduce or prevent associated complications of these disorders. © 2016 Wiley Periodicals, Inc.

The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Costales J, Kolevzon A. Neurosci Biobehav Rev. 2016;63:207-222. PMID: 26780584, PMCID: PMC4790729.

Autism and the synapse: emerging mechanisms and mechanism-based therapies. Ebrahimi-Fakhari D, Sahin M. Curr Opin Neurol. Apr 2015;28(2):91-102. PMID: 25695134.

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder. Tilot AK, Frazier TW 2nd, Eng C. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):609-619. PMID: 25916396, PMCID: PMC4489960.

Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex. Sundberg M, Sahin M. J Child Neurol. Aug 24 2015. PMID: 26303409, PMCID: PMC4644486.

Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits. He X, Thacker S, Romigh T, Yu Q, Frazier TW Jr, Eng C. Mol Autism. 2015 Nov 17;6:63. doi: 10.1186/s13229-015-0056-6. eCollection 2015.

Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Sahin M, Sur M. Science. Nov 20 2015;350(6263). PMID: 26472761, PMCID: PMC4739545.

Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity. Hussain SA, Kwong G, Millichap JJ, Mytinger JR, Ryan N, Matsumoto JH, Wu JY, Lerner JT, Sankar R. Epilepsia. 2015 Jan;56(1):77-81. doi: 10.1111/epi.12861. Epub 2014 Nov 10.

Improved fidelity of brain microstructure mapping from single-shell diffusion MRI. Taquet M, Scherrer B, Boumal N, Peters JM, Macq B, Warfield SK. Med Image Anal. Dec 2015;26(1):268- 286. PMID: 26529580, PMCID: PMC4679640.

Longitudinal changes in diffusion properties in white matter pathways of children with tuberous sclerosis complex. Baumer FM, Song JW, Mitchell PD, Pienaar R, Sahin M, Grant PE, Takahashi E. Pediatr Neurol. Jun 2015;52(6):615-623. PMID: 25817702, PMCID: PMC4442035.

Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. Tyburczy ME, Dies KA, Glass J, Camposano S, Chekaluk Y, Thorner AR, Lin L, Krueger D, Franz DN, Thiele EA, Sahin M, Kwiatkowski DJ. PLoS Genet. 2015 Nov 5;11(11):e1005637. doi: 10.1371/journal.pgen.1005637. eCollection 2015 Nov.

Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families. Frazier TW, Youngstrom EA, Hardan AY, Georgiades S, Constantino JN, Eng C. Mol Autism. 2015 Oct 27;6:58. doi: 10.1186/s13229-015-0050-z. eCollection 2015.

Therapeutic Advances in Autism and Other Neurodevelopmental Disorders. Neul JL, Sahin M. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):519-520. PMID: 26076992, PMCID: PMC4489958.

Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism. Davis PE, Peters JM, Krueger DA, Sahin M. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. Jul 2015;12(3):572-583. PMID: 25986747, PMCID: PMC4489948.

The neurology of mTOR. Lipton JO, Sahin M. Neuron. Oct 22 2014;84(2):275-291. PMID: 25374355, PMCID: PMC4223653.

The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm. Kilic-Berkmen G, Kim H, Chen D, Yeo CI, Dinasarapu AR, Scorr LM, Yeo WH, Peterson DA, Williams H, Ruby A, Mills R, Jinnah HA. Mov Disord. 2024 Feb 3. doi: 10.1002/mds.29734. Epub ahead of print. PMID: 38310362.

Blepharospasm is a type of dystonia (involuntary muscle twitching) which affects the muscles surrounding both eyes, causing forced blinking, eye irritation, and involuntary closure of the eyes. Although blepharospasm can be treated with a medication called botulinum toxin, outcomes are often inconsistent.

In this study, researchers conducted an exploratory, randomized, double-blind clinical trial of the oral drug dipraglurant for blepharospasm. Fifteen individuals with blepharospasm received either a placebo or dipraglurant. The team used multiple scales rated by clinicians or participants, digital video, and a wearable sensor to assess outcomes.

Results show that although dipraglurant was well tolerated in study participants, it did not produce an obvious benefit. Authors note that these results provide valuable information for planning future trials in blepharospasm.

Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach. Younce JR, Cascella RH, Berman BD, Jinnah HA, Bellows S, Feuerstein J, Wagle Shukla A, Mahajan A, Chang FCF, Duque KR, Reich S, Richardson SP, Deik A, Stover N, Luna JM, Norris SA. Dystonia. 2023;2:11305. doi: 10.3389/dyst.2023.11305. Epub 2023 Jun 8. PMID: 37920445; PMCID: PMC10621194

Dystonia is a neurological disorder characterized by excessive muscle contractions leading to abnormal postures, movements, and pain. Any region of the body can be involved, either in isolation or in combination with another region of the body. Although accurate classification of these combinations is important to providing care, it can sometimes be inconsistent.

In this study, researchers used a data-driven clustering approach to investigate which combinations are most common in dystonia. The team analyzed 1,618 participants with isolated non-focal dystonia from the Dystonia Coalition database to explore which body regions were affected together.

Results reinforce common patterns in cranial and cervical regions. However, findings also show unexpectedly strong associations between bilateral upper or lower limbs, revealing new patterns that may represent an underrecognized dystonia subtype.

Assessing the Severity of Cervical Dystonia: Ask the Doctor or Ask the Patient. Cotton AC, Scorr L, McDonald W, Comella C, Perlmutter JS, Goetz CG, Jankovic J, Marsh L, Factor S, Jinnah HA. Mov Disord Clin Pract. 2023 Aug 3;10(9):1399-1403. doi: 10.1002/mdc3.13827. PMID: 37772296; PMCID: PMC10525044

Cervical dystonia is a rare, often painful, movement disorder associated with characteristic sustained or jerky involuntary muscle contractions of the neck. The severity of cervical dystonia can be assessed using either clinician-rated scales (CRS) or patient-rated outcome (PRO) tools. However, these two measures are often poorly correlated.   

In this study, researchers aimed to determine if the correlation between a CRS and PRO for the movement disorder of cervical dystonia improves by accounting for non-movement features. The team evaluated 209 patients with cervical dystonia using a CRS and a PRO.

The results revealed a weak correlation between the two measures, even when considering only the movement. However, the correlation improved with a model that included non-motor symptoms of pain, depression, and disability. These results suggest that assessing the movement disorder with a PRO should also include assessments of non-motor symptoms that may contribute to the patient’s perception of the disorder. Findings may apply to other disorders, especially those with frequent non-motor co-morbidities.

Determinants of gait dystonia severity in cerebral palsy. Aravamuthan BR, Pearson TS, Ueda K, Miao H, Zerafati-Jahromi G, Gilbert L, Comella C, Perlmutter JS. Dev Med Child Neurol. 2023 Jul;65(7):968-977. doi: 10.1111/dmcn.15524. Epub 2023 Jan 26.

Interrater reliability of motor severity scales for hemifacial spasm. Lee HY, Park I, Luu MP, Zhao J, Vu JP, Cisneros E, Berman BD, Jinnah HA, Kim HJ, Liu CY, Perlmutter JS, Richardson SP, Weissbach A, Stebbins GT, Peterson DA. J Neural Transm (Vienna). 2023 Oct;130(10):1269-1279. doi: 10.1007/s00702-023-02667-w. Epub 2023 Jul 19.

Longitudinal predictors of health-related quality of life in isolated dystonia. Junker J, Hall J, Berman BD, Vidailhet M, Roze E, Bäumer T, Malaty IA, Shukla AW, Jankovic J, Reich SG, Espay AJ, Duque KR, Patel N, Perlmutter JS, Jinnah HA; Dystonia Coalition Study Group; Brandt V, Brüggemann N. J Neurol. 2023 Oct 15. doi: 10.1007/s00415-023-12022-4. Online ahead of print.

Pain Reduction in Cervical Dystonia Following Treatment with IncobotulinumtoxinA: A Pooled Analysis. Albanese A, Wissel J, Jost WH, Castagna A, Althaus M, Comes G, Scheschonka A, Vacchelli M, Jinnah HA. Toxins (Basel). 2023 May 12;15(5):333. doi: 10.3390/toxins15050333.

Suitability of Automated Writing Measures for Clinical Trial Outcome in Writer's Cramp. Bukhari-Parlakturk N, Lutz MW, Al-Khalidi HR, Unnithan S, Wang JE, Scott B, Termsarasab P, Appelbaum LG, Calakos N. Mov Disord. 2023 Jan;38(1):123-132. doi: 10.1002/mds.29237. Epub 2022 Oct 13.

Thyroid disease in cervical dystonia. Kilic-Berkmen G, Scorr L, Rosen A, Wu E, Freeman A, Silver M, Hanfelt J, Jinnah HA. Parkinsonism Relat Disord. 2023 Feb;107:105274. doi: 10.1016/j.parkreldis.2022.105274. Epub 2022 Dec 30. PMID: 36621155.

What Is Hemidystonia. Vizcarra JA, Jinnah HA. Mov Disord Clin Pract. 2023 Feb 3;10(3):477-481. doi: 10.1002/mdc3.13659. eCollection 2023 Mar.

Abnormalities of neural stem cells in Lesch-Nyhan disease. Dinasarapu AR, Sutcliffe DJ, Seifar F, Visser JE, Jinnah HA. J Neurogenet. 2022 Mar-Jun;36(2-3):81-87. doi: 10.1080/01677063.2022.2129632. Epub 2022 Oct 13.

Bidding for a Grateful Patient. Perlmutter JS. Narrat Inq Bioeth. 2022;12(1):7-9. doi: 10.1353/nib.2022.0003.

Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review. Scorr LM, Cho HJ, Kilic-Berkmen G, McKay JL, Hallett M, Klein C, Baumer T, Berman BD, Feuerstein JS, Perlmutter JS, Berardelli A, Ferrazzano G, Wagle-Shukla A, Malaty IA, Jankovic J, Bellows ST, Barbano RL, Vidailhet M, Roze E, Bonnet C, Mahajan A, LeDoux MS, Fung VSC, Chang FCF, Defazio G, Ercoli T, Factor S, Wojno T, Jinnah HA. Dystonia. 2022;1:10359. doi: 10.3389/dyst.2022.10359. Epub 2022 May 16.

Clinical and Structural Findings in Patients With Lesion-Induced Dystonia: Descriptive and Quantitative Analysis of Published Cases. Corp DT, Greenwood CJ, Morrison-Ham J, Pullinen J, McDowall GM, Younger EFP, Jinnah HA, Fox MD, Joutsa J. Neurology. 2022 Nov 1;99(18):e1957-e1967. doi: 10.1212/WNL.0000000000201042. Epub 2022 Aug 17.

Clinical features, pathophysiology, treatment, and controversies of tremor in dystonia. Panyakaew P, Jinnah HA, Shaikh AG. J Neurol Sci. 2022 Apr 15;435:120199. doi: 10.1016/j.jns.2022.120199. Epub 2022 Feb 22. PMID: 35259651.

Dystonia is a general term for a group of movement disorders characterized by uncontrollable, sometimes painful, involuntary muscle contractions, resulting in repetitive shaking, turning, and twisting of affected body parts. Dystonia is a rare disorder, but it often coexists with a more common disorder, tremor. The reasons for the frequent co-occurrence of dystonia and tremor are not clear. In this review article, researchers outline the differences in definitions, subtypes, and pathophysiology of dystonia and tremor. They outline some controversial topics, such as whether these two problems share a similar pathophysiology.

Correlating perceptual voice quality in ADSD with computer vision assessment of glottal geometry dynamics. Peterson QA, Fei T, Sy LE, Froeschke LLO, Mendelsohn AH, Berke GS, Peterson DA. J Speech Lang Hear Res. 2022 Oct 17;65(10):3695-3708. doi: 10.1044/2022_JSLHR-22-00053. Epub 2022 Sep 21.

Diagnosis and classification of blepharospasm: Recommendations based on empirical evidence. Kilic-Berkmen G, Defazio G, Hallett M, Berardelli A, Ferrazzano G, Belvisi D, Klein C, Bäumer T, Weissbach A, Perlmutter JS, Feuerstein J, Jinnah HA; Dystonia Coalition Investigators. J Neurol Sci. 2022 Aug 15;439:120319. doi: 10.1016/j.jns.2022.120319. Epub 2022 Jun 10. PMID: 35716653; PMCID: PMC9357089.

Blepharospasm is a rare disorder characterized by spasms of muscles surrounding both eyes with excessive blinking and squinting. It is the second most common form of dystonia (involuntary muscle twitching) and often spreads to other regions of the body. Currently, guidelines for diagnosis and classification are ambiguous. In this study, researchers aimed to provide more specific recommendations for diagnosis and classification of blepharospasm. Data were obtained from the Dystonia Coalition for patients diagnosed with all types of isolated dystonia. The team evaluated these data to determine how examinations recorded by movement disorder specialists were used to classify blepharospasm as focal, segmental, or multifocal. Results showed much variability in expert opinion regarding the diagnosis of blepharospasm, which was often inconsistent with existing guidelines for the diagnosis and classification of focal blepharospasm. This study highlights the need for more specific guidelines, which are provided in the publication.

Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice. Hauser RA, Meyer JM, Factor SA, Comella CL, Tanner CM, Xavier RM, Caroff SN, Lundt L. CNS Spectr. 2022 Apr;27(2):208-217. doi: 10.1017/S109285292000200X. Epub 2020 Nov 20.

From null to midline: changes in head posture do not predictably change head tremor in cervical dystonia. Vu JP, Cisneros E, Zhao J, Lee HY, Jankovic J, Factor SA, Goetz CG, Barbano RL, Perlmutter JS, Jinnah HA, Richardson SP, Stebbins GT, Elble RJ, Comella CL, Peterson DA. Dystonia. 2022;1:10684. doi: 10.3389/dyst.2022.10684. Epub 2022 Sep 1.

Head tremor in cervical dystonia: Quantifying severity with computer vision. Vu JP, Cisneros E, Lee HY, Le L, Chen Q, Guo XA, Rouzbehani R, Jankovic J, Factor S, Goetz CG, Barbano RL, Perlmutter JS, Jinnah HA, Pirio Richardson S, Stebbins GT, Elble R, Comella CL, Peterson DA. J Neurol Sci. 2022 Mar 15;434:120154. doi: 10.1016/j.jns.2022.120154. Epub 2022 Jan 22.

Hold that pose: capturing cervical dystonia's head deviation severity from video. Zhang Z, Cisneros E, Lee HY, Vu JP, Chen Q, Benadof CN, Whitehill J, Rouzbehani R, Sy DT, Huang JS, Sejnowski TJ, Jankovic J, Factor S, Goetz CG, Barbano RL, Perlmutter JS, Jinnah HA, Berman BD, Richardson SP, Stebbins GT, Comella CL, Peterson DA. Ann Clin Transl Neurol. 2022 Mar 25. doi: 10.1002/acn3.51549. Epub ahead of print. PMID: 35333449.

Cervical dystonia (CD) is a movement disorder resulting in characteristic, sustained, or tremor-like involuntary muscle contractions of the neck. It is characterized by excessive pulling of the muscles of the neck and shoulder, which causes the head to turn or tilt involuntarily. Typically, head posture severity is quantified with clinical rating scales that are susceptible to variability, reducing their sensitivity as outcome measures. Previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. In this study, researchers evaluated a novel software system—the Computational Motor Objective Rater (CMOR)—to quantify multi-axis directionality and severity of head posture in CD using only conventional video camera recordings. They found that CMOR’s metrics for head posture severity correlated with clinical rating scales. Authors note that CMOR’s reliance upon only conventional video recordings supports its future potential for large-scale multisite clinical trials.

Measurement Properties of Clinical Scales Rating the Severity of Blepharospasm: A Multicenter Observational Study. Defazio G, Hallett M, Berardelli A, Perlmutter JS, Berman BD, Jankovic J, Bäumer T, Comella C, Ercoli T, Ferrazzano G, Fox SH, Kim HJ, Moukheiber ES, Pirio Richardson S, Weissbach A, Gigante AF, Jinnah HA. Mov Disord Clin Pract. 2022 Aug 15;9(7):949-955. doi: 10.1002/mdc3.13530. eCollection 2022 Oct.

Microstructural white matter abnormalities in Lesch-Nyhan disease. Del Bene VA, Crawford JL, Gómez-Gastiasoro A, Vannorsdall TD, Buchholz A, Ojeda N, Harris JC, Jinnah HA, Schretlen DJ. Eur J Neurosci. 2022 Jan;55(1):264-276. doi: 10.1111/ejn.15512. Epub 2021 Dec 6.

Motor and psychiatric features in idiopathic blepharospasm: A data-driven cluster analysis. Defazio G, Gigante AF, Hallett M, Berardelli A, Perlmutter JS, Berman BD, Jankovic J, Bäumer T, Comella C, Ercoli T, Ferrazzano G, Fox SH, Kim HJ, Moukheiber ES, Richardson SP, Weissbach A, Jinnah HA.. Parkinsonism Relat Disord. 2022 Nov;104:94-98. doi: 10.1016/j.parkreldis.2022.10.008. Epub 2022 Oct 13.

Protracted course progressive supranuclear palsy. Couto B, Martinez-Valbuena I, Lee S, Alfradique-Dunham I, Perrin RJ, Perlmutter JS, Cruchaga C, Kim A, Visanji N, Sato C, Rogaeva E, Lang AE, Kovacs GG. Eur J Neurol. 2022 Aug;29(8):2220-2231. doi: 10.1111/ene.15346. Epub 2022 Apr 21.

Reid EW. Reid EW, Nobriga CV. Clin Linguist Phon. 2022 Jul 12:1-16. doi: 10.1080/02699206.2022.2096483. Online ahead of print.

The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes. Di Fonzo A, Albanese A, Jinnah HA. Curr Opin Neurol. 2022 Aug 1;35(4):502-509. doi: 10.1097/WCO.0000000000001076. Epub 2022 Jul 5. PMID: 35856917; PMCID: PMC9309988.

The dystonias are a group of movement disorders characterized by uncontrollable, sometimes painful, involuntary muscle contractions, resulting in repetitive shaking, turning, and twisting of affected body parts. As new genetic causes continue to be discovered, researchers have found that these different genetic forms share unexpectedly common underlying mechanisms. In this review article, authors explore the phenotypic diversity and shared mechanisms across dystonia syndromes. They also describe how these mechanisms can give rise to motor performance dysfunctions with a clinical aspect of dystonia. Authors state that this relationship between dystonia genes could revolutionize current dystonia classification systems. In the future, these advances could have promising effects on mechanism-based therapeutic approaches.

Uric Acid in Parkinson's Disease: What Is the Connection?. Seifar F, Dinasarapu AR, Jinnah HA.. Mov Disord. 2022 Nov;37(11):2173-2183. doi: 10.1002/mds.29209. Epub 2022 Sep 3.

A Multi-center Genome-wide Association Study of Cervical Dystonia. Sun YV, Li C, Hui Q, Huang Y, Barbano R, Rodriguez R, Malaty IA, Reich S, Bambarger K, Holmes K, Jankovic J, Patel NJ, Roze E, Vidailhet M, Berman BD, LeDoux MS, Espay AJ, Agarwal P, Pirio-Richardson S, Frank SA, Ondo WG, Saunders-Pullman R, Chouinard S, Natividad S, Berardelli A, Pantelyat AY, Brashear A, Fox SH, Kasten M, Krämer UM, Neis M, Bäumer T, Loens S, Borsche M, Zittel S, Maurer A, Gelderblom M, Volkmann J, Odorfer T, Kühn AA, Borngräber F, König IR, Cruchaga C, Cotton AC, Kilic-Berkmen G, Freeman A, Factor SA, Scorr L, Bremner JD, Vaccarino V, Quyyumi AA, Klein C, Perlmutter JS, Lohmann K, Jinnah HA. Mov Disord. 2021 Jul 28. doi: 10.1002/mds.28732. Online ahead of print.

Cervical dystonia is a painful condition in which a patient’s neck muscles contract involuntarily, causing the head to twist or turn to one side. In this multi-center international study, researchers conducted a Genome-Wide Association Study (GWAS) using samples from the Dystonia Coalition Biorepository. They compared 919 cervical dystonia patients with 1491 controls, seeking to identify genetic loci—fixed positions on a chromosome where a particular gene or genetic marker is located—related to the disorder. They identified one genome-wide significant variant that was however not replicated in an independent sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia. One low-frequency variant located within the GABBR2 gene on chromosome 9 was associated with lower age-at-onset. Authors concluded that the genetic underpinnings of cervical dystonia are heterogeneous and likely consist of multiple distinct variants of small effect sizes, rather than one gene that is responsible for many cases. Larger GWAS sample sizes may be needed to understand the genetic causes of cervical dystonia.

Cervical Dystonia Is Associated with Aberrant Inhibitory Signaling Within the Thalamus. Groth CL, Brown M, Honce JM et al. Front Neurol. 2021; 11: 575879. PMCID: PMC7900407.

Current Guidelines for Classifying and Diagnosing Cervical Dystonia: Empirical Evidence and Recommendations. Kilic-Berkmen G, Pirio Richardson S, Perlmutter JS et al. MDCP, Nov 2021. https://doi.org/10.1002/mdc3.13376. PMCID: in progress.

Deep brain stimulation in Lesch-Nyhan disease: outcomes from the patient's perspective. Visser JE, Cotton AC, Schretlen DJ, Bloch J, Tedroff K, Schechtmann G, Radu Djurfeldt D, Gonzalez V, Cif L, Jinnah HA. Dev Med Child Neurol. 2021 Mar 10. doi: 10.1111/dmcn.14852. Online ahead of print.

Diagnostic criteria for blepharospasm: A multicenter international study. Defazio G, Jinnah HA, Berardelli A, Perlmutter JS, Berkmen GK, Berman BD, Jankovic J, Bäumer T, Comella C, Cotton AC, Ercoli T, Ferrazzano G, Fox S, Kim HJ, Moukheiber ES, Richardson SP, Weissbach A, Wrigth LJ, Hallett M. Parkinsonism Relat Disord. 2021 Oct;91:109-114. doi: 10.1016/j.parkreldis.2021.09.004. Epub 2021 Sep 8. PMID: 34583301.

Blepharospasm (BSP) is a form of focal dystonia that manifests with eyelid spasms, involuntary eyelid closures, and spontaneous blinking. To date, there are no widely accepted criteria to diagnose BSP. In this study, researchers validate the use of new diagnostic criteria for BSP in a diverse international population. “This was a huge, multicenter effort aimed at establishing internationally acceptable diagnostic criteria for BSP,” says H. A. Jinnah, MD, PhD, principal investigator of the DC. “Such criteria did not exist before. What we do in the USA with RDCRN funding must ultimately go to the rest of the world.”

Distinct progression patterns across Parkinson disease clinical subtypes. Myers PS, Jackson JJ, Clover AK, Lessov-Schlaggar CN, Foster ER, Maiti B, Perlmutter JS, Campbell MC. Ann Clin Transl Neurol. 2021 Aug;8(8):1695-1708. doi: 10.1002/acn3.51436. Epub 2021 Jul 26.

Does raising the arms modify head tremor severity in cervical dystonia?. Cisneros E, Vu JP, Lee HY et al. Tremor and Other Hyperkinetic Movements. 2021. doi: 10.5334/tohm.623. PMCID: PMC8231450.

Dystonia and Tremor: A Cross-Sectional Study of the Dystonia Coalition Cohort. Shaikh AG, Beylergil SB, Scorr L, Kilic-Berkmen G, Freeman A, Klein C, Junker J, Loens S, Brüggemann N, Münchau A, Bäumer T, Vidailhet M, Roze E, Bonnet C, Jankovic J, Jimenez-Shahed J, Patel N, Marsh L, Comella C, Barbano RL, Berman BD, Malaty I, Wagle Shukla A, Reich SG, Ledoux MS, Berardelli A, Ferrazzano G, Stover N, Ondo W, Pirio Richardson S, Saunders-Pullman R, Mari Z, Agarwal P, Adler C, Chouinard S, Fox SH, Brashear A, Truong D, Suchowersky O, Frank S, Factor S, Perlmutter J, Jinnah HA. Neurology. 2021 Jan 26;96(4):e563-e574. doi: 10.1212/WNL.0000000000011049. Epub 2020 Oct 12.

Feedback-dependent neuronal properties make focal dystonias so focal. Sedov A, Usova S, Popov V, Tomskiy A, Jinnah HA, Shaikh AG. Eur J Neurosci. 2021 Apr;53(7):2388-2397. doi: 10.1111/ejn.14933. Epub 2020 Aug 31.

Seeking to better understand the neuron activity responsible for dystonia, researchers tested the hypothesis that focal dystonia (a condition that causes abnormal movements in a single body part) may be associated with specific vs broad neuronal abnormalities. They measured the activity of individual neurons of the basal ganglia during deep brain stimulation surgery in 12 patients with dystonia limited to the neck. They found abnormal neuronal activity for both neck and hand neurons, even though the hand was unaffected. These results imply abnormalities of neuronal activity are not restricted to neurons associated with the affected body region, but appear to be more widespread. Symptoms may appear in only in specific body regions, such as the neck, when a second abnormality is added, such as sensory feedback from the affected region.

Functional Connectivity of Vermis Correlates with Future Gait Impairments in Parkinson's Disease. Maiti B, Rawson KS, Tanenbaum AB, Koller JM, Snyder AZ, Campbell MC, Earhart GM, Perlmutter JS. Mov Disord. 2021 Nov;36(11):2559-2568. doi: 10.1002/mds.28684. Epub 2021 Jun 10.

Head tremor and pain in cervical dystonia. Vu JP, Lee HY, Chen Q, Cisneros E, Barbano RL, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Berman BD, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. J Neurol. 2021 May;268(5):1945-1950. doi: 10.1007/s00415-020-10378-5. Epub 2021 Jan 8.

To determine how head tremor and pain are associated with cervical dystonia, researchers undertook a retrospective review of severity and pain rating scales from 188 patients. They examined associations of head trauma and pain with age at onset, disease duration, and head tremor subtype, finding that head tremor severity was associated with longer disease duration while pain severity was associated with younger age at onset. Researchers said these associations further characterize the heterogeneity of cervical dystonia’s clinical presentation and suggest similarly heterogenous underlying mechanisms.

Induced pluripotent stem cells from subjects with Lesch-Nyhan disease. Sutcliffe DJ, Dinasarapu AR, Visser JE, Hoed JD, Seifar F, Joshi P, Ceballos-Picot I, Sardar T, Hess EJ, Sun YV, Wen Z, Zwick ME, Jinnah HA. Sci Rep. 2021 Apr 19;11(1):8523. doi: 10.1038/s41598-021-87955-9.

Is Levodopa Response a Valid Indicator of Parkinson's Disease?. Martin WRW, Miles M, Zhong Q, Hartlein J, Racette BA, Norris SA, Ushe M, Maiti B, Criswell S, Davis AA, Kotzbauer PT, Cairns NJ, Perrin RJ, Perlmutter JS. Mov Disord. 2021 Apr;36(4):948-954. doi: 10.1002/mds.28406. Epub 2020 Nov 30.

Neuropathology of blepharospasm. Fagan M, Scorr L, Bernhardt D, Hess EJ, Perlmutter JS, Pardo CA, Jinnah HA. Exp Neurol. 2021 Dec;346:113855. doi: 10.1016/j.expneurol.2021.113855. Epub 2021 Aug 28. PMID: 34464652; PMCID: PMC8490317.

The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal repetitive movements or postures. Blepharospasm is a subtype of dystonia characterized by overactive facial muscles. Previous brain imaging studies have implied subtle structural changes in blepharospasm, but the nature of these changes is not well understood. In this study, researchers found subtle loss of cerebellar Purkinje neurons in histopathological studies of brains from blepharospasm cases. These findings are similar to those reported for subjects with cervical dystonia. “To focus on what we should be looking for in blepharospasm, we used what we learned about cervical dystonia published in 2013 in a prior funding cycle,” says H. A. Jinnah, MD, PhD, principal investigator of the DC. “Thus, the RDCRN strategy of combining similar disorders under the same research umbrella is successful in facilitating both the research questions and methodologies.”

Non-motor phenotypic subgroups in adult-onset idiopathic, isolated, focal cervical dystonia. Megan E Wadon, Grace A Bailey, Zehra Yilmaz, Emily Hubbard, Meshari AlSaeed, Amy Robinson, Duncan McLauchlan, Richard L Barbano, Laura Marsh, Stewart A Factor, Susan H Fox, Charles H Adler, Ramon L Rodriguez, Cynthia L Comella, Stephen G Reich, William L Severt, Christopher G Goetz, Joel S Perlmutter, Hyder A Jinnah, Katharine E Harding, Cynthia Sandor, Kathryn J Peall. Brain and Behavior. 11,e2292. https://doi.org/10.1002/brb3.2292.

Adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD) is a disorder characterized by involuntary muscle contractions that cause repetitive movements or abnormal postures. These movements can be painful and cause considerable disability. Although patients most commonly present to clinical services due to their motor symptoms, increasing evidence suggests a significant non-motor phenotype to be associated with most forms of dystonia, including AOIFCD. Improved understanding of these non-motor symptoms is needed to better target therapeutic interventions. In this study, researchers examined non-motor phenotypic features to identify possible AOIFCD subgroups. Non-motor symptoms were assessed in participants with AOIFCD, including psychiatric symptoms, pain, sleep disturbance, and quality of life. To investigate the relationship between these symptoms and determine phenotypic subgroups, researchers used Cluster and Bayesian multiple mixed model phenotype analyses. They identified two phenotypic subgroups of non-motor symptoms accompanying AOIFCD, with differences in psychiatric symptoms, pain catastrophizing, sleep quality, and quality of life. Researchers say that improved understanding of these symptom groups will enable better targeted pathophysiological investigation and future therapeutic intervention.

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases. Scorr LM, Factor FA, Parra SP et al and Jinnah HA for the Dystonia Coalition Investigators. Front Neurol. 2021. https://doi.org/10.3389/fneur.2021.700714. PMCID: in progress.

Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia. Sedov A, Popov V, Gamaleya A, Semenova U, Tomskiy A, Jinnah HA, Shaikh AG. Clin Neurophysiol 2021; 132: 3190-3196. PMCID: in progress.

Predictive modeling of spread in adult-onset isolated dystonia: key properties and effect of tremor inclusion. Wang M, Sajobi T, Morgante F, Adler C, Agarwal P, Bäumer T, Berardelli A, Berman BD, Blumin J, Borsche M, Brashear A, Deik A, Duque K, Espay AJ, Ferrazzano G, Feuerstein J, Fox S, Frank S, Hallett M, Jankovic J, LeDoux MS, Leegwater-Kim J, Mahajan A, Malaty IA, Ondo W, Pantelyat A, Pirio-Richardson S, Roze E, Saunders-Pullman R, Suchowersky O, Truong D, Vidailhet M, Shukla AW, Perlmutter JS, Jinnah HA, Martino D. European Journal of Neurology. 2021 Dec;28(12):3999-4009. doi: 10.1111/ene.15031. Epub 2021 Aug 4. PMID: 34296504; PMCID: PMC9100858.

Quality of life in isolated dystonia: non-motor manifestations matter. Junker J, Berman BD, Hall J, Wahba DW, Brandt V, Perlmutter JS, Jankovic J, Malaty IA, Wagle Shukla A, Reich SG, Espay AJ, Duque KR, Patel N, Roze E, Vidailhet M, Jinnah HA, Brüggemann N. J Neurol Neurosurg Psychiatry 2021 Feb 9; jnnp-2020-325193. doi: 10.1136/jnnp-2020-325193. Online ahead of print. PMCID: PMC8356023.

Rational Design of Novel Therapies for Pantothenate Kinase-Associated Neurodegeneration. Thakur N, Klopstock T, Jackowski S, Kuscer E, Tricta F, Videnovic A, Jinnah HA. Mov Disord. 2021 Sep;36(9):2005-2016. doi: 10.1002/mds.28642. Epub 2021 May 18.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurogenetic disorder in which specific regions of the central nervous system progressively degenerate, causing progressive, abnormal, involuntary movements. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in enzyme activity. This disruption allows iron to accumulate in the brain. Increased understanding of the molecular and biochemical mechanisms of the disease has allowed researchers to use these insights to begin designing new therapeutics for the disorder. Study authors review the results of recent clinical trials and pre-clinical studies of several compounds currently being evaluated. They say that these trials have helped improve trial designs and allowed the development of PKAN-specific measures to monitor outcomes. They conclude that PKAN provides a good model for targeted drug development and clinical trial design for rare disorders.

Resting-State Functional Connectivity Predicts STN DBS Clinical Response. Younce JR, Campbell MC, Hershey T, Tanenbaum AB, Milchenko M, Ushe M, Karimi M, Tabbal SD, Kim AE, Snyder AZ, Perlmutter JS, Norris SA. Mov Disord. 2021 Mar;36(3):662-671. doi: 10.1002/mds.28376. Epub 2020 Nov 19.

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies. Kilic-Berkmen G, Wright LJ, Perlmutter JS, Comella C, Hallett M, Teller J, Pirio Richardson S, Peterson DA, Cruchaga C, Lungu C, Jinnah HA. Front Neurol. 2021. 8;12:660909. doi: 10.3389/fneur.2021.660909. PMCID: PMC8060489. [Review]

The emerging neurological spectrum of AARS2-associated disorders. Parra SP, Heckers SH, Wilcox WR, Mcknight CD, Jinnah HA.. Parkinsonism Relat Disord. 2021 Dec;93:50-54. doi: 10.1016/j.parkreldis.2021.10.031. Epub 2021 Nov 10.

A metabolomic study of cervical dystonia. Liu C, Scorr L, Kilic-Berkmen G, Cotton A, Factor SA, Freeman A, Tran V, Liu K, Uppal K, Jones D, Jinnah HA, Sun YV. Parkinsonism Relat Disord. 2021 Jan;82:98-103. doi: 10.1016/j.parkreldis.2020.11.020. Epub 2020 Nov 26. PMID: 33271463; PMCID: PMC7856090.

Cervical dystonia is the most common adult-onset focal dystonia. Researchers currently believe that cervical dystonia may be caused by a combination of genetic and environmental factors. Although genetic factors have been studied extensively, other factors have not. To identify potentially abnormal metabolites or altered biological pathways, researchers conducted an exploratory metabolomics analysis of cervical dystonia. The team compared plasma samples from 100 idiopathic cervical dystonia patients and 100 controls. Results showed that altered biological pathways may relate to carbohydrate and lipid metabolism. Study authors say this may provide novel insights into the biology of cervical dystonia.

Clinical and Demographic Characteristics of Upper Limb Dystonia. Norris SA, Jinnah HA, Klein C, Jankovic J, Berman BD, Roze E, Mahajan A, Espay AJ, Murthy AV, Fung VSC, LeDoux MS, Chang FCF, Vidailhet M, Testa C, Barbano R, Malaty IA, Bäumer T, Loens S, Wright LJ, Perlmutter JS. Mov Disord. 2020 Nov;35(11):2086-2090. doi: 10.1002/mds.28223. Epub 2020 Aug 26.

Hemodynamic responses are abnormal in isolated cervical dystonia. Berman BD, Groth CL, Shelton E, Sillau SH, Sutton B, Legget KT, Tregellas JR. J Neurosci Res. 2020 Apr;98(4):692-703. doi: 10.1002/jnr.24547. Epub 2019 Nov 6.

It's tricky: Rating alleviating maneuvers in cervical dystonia. Cisneros E, Stebbins GT, Chen Q, Vu JP, Benadof CN, Zhang Z, Barbano RL, Fox SH, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Adler CH, Factor SA, Reich SG, Rodriguez R, Severt LL, Stover NP, Berman BD, Comella CL, Peterson DA. J Neurol Sci. 2020 Dec 15;419:117205. doi: 10.1016/j.jns.2020.117205. Epub 2020 Nov 1.

Medical and Surgical Treatments for Dystonia. Jinnah HA. Neurol Clin. 2020 May;38(2):325-348. doi: 10.1016/j.ncl.2020.01.003. Epub 2020 Mar 2.

Pallidal Activity in Cervical Dystonia with and Without Head Tremor. Sedov A, Usova S, Semenova U, Gamaleya A, Tomskiy A, Beylergil SB, Jinnah HA, Shaikh AG. Cerebellum. 2020 Jun;19(3):409-418. doi: 10.1007/s12311-020-01119-5.

Postural Directionality and Head Tremor in Cervical Dystonia. Chen Q, Vu JP, Cisneros E, Benadof CN, Zhang Z, Barbano RL, Goetz CG, Jankovic J, Jinnah HA, Perlmutter JS, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. Tremor Other Hyperkinet Mov (N Y). 2020 Jan 20;10. doi: 10.7916/tohm.v0.745. eCollection 2020.

Regional, not global, functional connectivity contributes to isolated focal dystonia. Norris SA, Morris AE, Campbell MC, Karimi M, Adeyemo B, Paniello RC, Snyder AZ, Petersen SE, Mink JW, Perlmutter JS. Neurology. 2020 Oct 20;95(16):e2246-e2258. doi: 10.1212/WNL.0000000000010791. Epub 2020 Sep 10.

Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. Berman BD, Groth CL, Sillau SH, Pirio Richardson S, Norris SA, Junker J, Brüggemann N, Agarwal P, Barbano RL, Espay AJ, Vizcarra JA, Klein C, Bäumer T, Loens S, Reich SG, Vidailhet M, Bonnet C, Roze E, Jinnah HA, Perlmutter JS. J Neurol Neurosurg Psychiatry. 2020 Mar;91(3):314-320. doi: 10.1136/jnnp-2019-321794. Epub 2019 Dec 17.

Soft Nanomembrane Sensors and Flexible Hybrid Bioelectronics for Wireless Quantification of Blepharospasm. Mahmood M, Kwon S, Berkmen GK, Kim YS, Scorr L, Jinnah HA, Yeo WH. IEEE Trans Biomed Eng. 2020 Nov;67(11):3094-3100. doi: 10.1109/TBME.2020.2975773. Epub 2020 Feb 21.

The Influence of Linguistic Demand on Symptom Expression in Adductor Spasmodic Dysphonia. Laura LO Froeschke. Journal of Voice. 2020; 34: 807.e11-807.e21. PMCID: In Progress.

Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration. Marshall RD, Collins A, Escolar ML, Jinnah HA, Klopstock T, Kruer MC, Videnovic A, Robichaux-Viehoever A, Burns C, Swett LL, Revicki DA, Bender RH, Lenderking WR.. Orphanet J Rare Dis. 2019 Jul 12;14(1):174. doi: 10.1186/s13023-019-1142-1.

Gravity-Independent Upbeat Nystagmus in Syndrome of Anti-GAD Antibodies. Feldman D, Otero-Millan J, Shaikh AG. Cerebellum. 2019 Apr;18(2):287-290. doi: 10.1007/s12311-018-0972-z.

Head tremor at disease onset: an ataxic phenotype of cervical dystonia. Merola A, Dwivedi AK, Shaikh AG, Tareen TK, Da Prat GA, Kauffman MA, Hampf J, Mahajan A, Marsili L, Jankovic J, Comella CL, Berman BD, Perlmutter JS, Jinnah HA, Espay AJ. J Neurol. 2019 Aug;266(8):1844-1851. doi: 10.1007/s00415-019-09341-w. Epub 2019 Apr 26.

Involuntary Thumb Flexion on Neurological Examination: An Unusual Form of Upper Limb Dystonia in the Faroe Islands. Kim CY, Petersen MS, Eliasen EH et al. Tremor Other Hyperkinet Mov. 2019; 20: 9. PMCID: PMC6702791. [Research Support]

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. Fernandez HH, Stamler D, Davis MD, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Woods SW, Bega D, LeDoux MS, Shprecher DR, Anderson KE. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1317-1323. doi: 10.1136/jnnp-2018-319918. Epub 2019 Jul 10.

Naming Genes for Dystonia: DYT-z or Ditzy?. Mencacci NE and Jinnah HA. Tremor Other Hyperkinet Mov. 2019; 28: 9. PMCID: PMC6714488. [Research Support]

Past and Present of Eye Movement Abnormalities in Ataxia-Telangiectasia. Tang SY, Shaikh AG. Cerebellum. 2019 Jun;18(3):556-564. doi: 10.1007/s12311-018-0990-x.

Progressive Encephalomyelitis with Rigidity and Myoclonus Syndrome Presenting as Catatonia. Witek N, Hebert C, Gera A, Comella C. Psychosomatics. 2019; 60: 83-87. PMCID: In Progress.

Relationship between jerky and sinusoidal oscillations in cervical dystonia. Beylergil SB, Singh AP, Zee DS, Jinnah HA, Shaikh AG. Parkinsonism Relat Disord. 2019 Sep;66:130-137. doi: 10.1016/j.parkreldis.2019.07.024. Epub 2019 Jul 20.

Sensory Tricks Are Associated with Higher Sleep-Related Quality of Life in Cervical Dystonia. Benadof CN, Cisneros E, Appelbaum MI, Stebbins GT, Comella CL, Peterson DA. Tremor Other Hyperkinet Mov (N Y). 2019 Jun 17;9. doi: 10.7916/4q53-vt23. eCollection 2019.

Soft Material-Enabled, Active Wireless, Thin-Film Bioelectronics for Quantitative Diagnostics of Cervical Dystonia. Kwon YT, Lee Y, Berkmen GK, Lim HR, Scorr L, Jinnah HA, Yeo WH. Adv Mater Technol. 2019 Oct;4(10):1900458. doi: 10.1002/admt.201900458. Epub 2019 Aug 16.

The Dystonias. Jinnah HA. Continuum (Minneap Minn). 2019 Aug;25(4):976-1000. doi: 10.1212/CON.0000000000000747.

The role of pallidum in the neural integrator model of cervical dystonia. Sedov A, Usova S, Semenova U, Gamaleya A, Tomskiy A, Crawford JD, Corneil B, Jinnah HA, Shaikh AG. Neurobiol Dis. 2019 May;125:45-54. doi: 10.1016/j.nbd.2019.01.011. Epub 2019 Jan 22.

Tremor in chronic inflammatory demyelinating polyneuropathy: Proof of unifying network model for dystonia. Pyatka N, Sedov A, Walter BL et al. Prog Brain Res. 2019; 249: 285-294. PMCID: In progress.

A strategy for managing flu-like symptoms after botulinum toxin injections. George EB, Cotton AC, Shneyder N, Jinnah HA. J Neurol. 2018 Aug;265(8):1932-1933. doi: 10.1007/s00415-018-8934-4. Epub 2018 Jun 20.

Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia. Popa T, Hubsch C, James P et al. Nat Sci Rep. 2018; 8: 2263. PMCID: PMC5797249.

Cervical dystonia and substance abuse. Mahajan A, Jankovic J, Marsh L, Patel A, Jinnah HA, Comella C, Barbano R, Perlmutter J, Patel N; members of the Dystonia Coalition. J Neurol. 2018 Apr;265(4):970-975. doi: 10.1007/s00415-018-8840-9. Epub 2018 Mar 22.

Consensus-Based Attributes for Identifying Patients With Spasmodic Dysphonia and Other Voice Disorders. Ludlow CL, Domangue R, Sharma D, Jinnah HA, Perlmutter JS, Berke G, Sapienza C, Smith ME, Blumin JH, Kalata CE, Blindauer K, Johns M, Hapner E, Harmon A, Paniello R, Adler CH, Crujido L, Lott DG, Bansberg SF, Barone N, Drulia T, Stebbins G. JAMA Otolaryngol Head Neck Surg. 2018 Aug 1;144(8):657-665. doi: 10.1001/jamaoto.2018.0644.

Dysfunction in emotion processing underlies functional (psychogenic) dystonia. Espay AJ, Maloney T, Vannest J et al. Mov Disord. 2018; 33: 136-145. PMCID: PMC5767134.

Effects of deep brain stimulation on eye movements and vestibular function. Shaikh AG, Antoniades C, Fitzgerald J et al. Front Neurol. 2018; 9: 444. PMCID: PMC6005881.

Evolving concepts in the pathogenesis of dystonia. Jinnah HA, Hess EJ. Parkinsonism Relat Disord. 2018 Jan;46 Suppl 1(Suppl 1):S62-S65. doi: 10.1016/j.parkreldis.2017.08.001. Epub 2017 Aug 2.

Expert Opinion vs Patient Perspective in Treatment of Rare Disorders: Tooth Removal in Lesch-Nyhan Disease as an Example. Cotton AC, Bell RB, Jinnah HA. JIMD Rep. 2018;41:25-27. doi: 10.1007/8904_2017_80. Epub 2017 Dec 15.

Eye movement research in the twenty-first century-a window to the brain, mind, and more. Shaikh AG, Zee DS. Cerebellum. 2018; 17: 252-258. [Review] 

Functional imaging in dystonia. Norris SA, Perlmutter JS. In Treatment of Dystonia, ed Dressler, Altenmuller, & Krauss, Cambridge University Press, Cambridge, UK, June 2018, ISBN: 9781107132863. [Chapter]

In Vivo Characterization of Two (18)F-Labeled PDE10A PET Radioligands in Nonhuman Primate Brains. Liu H, Jin H, Luo Z, Yue X, Zhang X, Flores H, Su Y, Perlmutter JS, Tu Z. ACS Chem Neurosci. 2018 May 16;9(5):1066-1073. doi: 10.1021/acschemneuro.7b00458. Epub 2018 Feb 19.

Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?. Jinnah HA, Comella CL, Perlmutter J, Lungu C, Hallett M; Dystonia Coalition Investigators. Toxicon. 2018 Jun 1;147:89-95. doi: 10.1016/j.toxicon.2017.09.004. Epub 2017 Sep 6.

Minimal clinically important change in the Toronto Western Spasmodic Torticollis Rating Scale. Espay AJ, Trosch R, Suarez G et al. Parkinsonism Relat Disord. 2018; 52: 94-97. PMCID: In Progress.

Paraneoplastic seesaw nystagmus and opsoclonus provides evidence for hyperexcitable reciprocally innervating mesencephalic network. Rizvi MT, Cameron L, Kilbane C, Shaikh AG. J Neurol Sci. 2018 Jul 15;390:239-245. doi: 10.1016/j.jns.2018.05.002. Epub 2018 May 3.

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia. Shi LL, Simpson CB, Hapner ER, Jinnah HA, Johns MM 3rd. J Voice. 2018 Mar;32(2):234-238. doi: 10.1016/j.jvoice.2017.05.004. Epub 2017 Jun 23.

Physiological effects of subthalamic nucleus deep brain stimulation surgery in cervical dystonia. Wagle Shukla A, Ostrem JL, Vaillancourt DE et al. J Neurol Neurosurg Psychiatry. 2018; 89: 1296-1300. PMCID: PMC7498178.

Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia. Scorr LM, Silver MR, Hanfelt J, Sperin E, Freeman A, Jinnah HA, Factor SA. Neurotherapeutics. 2018 Apr;15(2):452-458. doi: 10.1007/s13311-018-0620-9.

Predictors of alcohol responsiveness in dystonia. Junker J, Brandt V, BD B, Vidailhet M et al. Neurology 2018; 91: 2020-2026. PMCID: PMC6260199.

Quantitative, clinically relevant acoustic measurements of focal embouchure dystonia. Morris AE, Norris SA, Perlmutter JS, Mink JW. Mov Disord. 2018 Mar;33(3):449-458. doi: 10.1002/mds.27298. Epub 2018 Feb 20.

The motor network model for dystonia. Jinnah HA, Hess EJ. In Treatment of dystonia. Cambridge University Press. 1st Edition, 2018. [Book chapter]

Treatable inherited rare movement disorders. Jinnah HA, Albanese A, Bhatia KP, Cardoso F, Da Prat G, de Koning TJ, Espay AJ, Fung V, Garcia-Ruiz PJ, Gershanik O, Jankovic J, Kaji R, Kotschet K, Marras C, Miyasaki JM, Morgante F, Munchau A, Pal PK, Rodriguez Oroz MC, Rodríguez-Violante M, Schöls L, Stamelou M, Tijssen M, Uribe Roca C, de la Cerda A, Gatto EM; International Parkinson's Disease Movement Disorders Society Task Force on Rare Movement Disorders. Mov Disord. 2018 Jan;33(1):21-35. doi: 10.1002/mds.27140. Epub 2017 Sep 1.

Vergence and strabismus in neurodegenerative disorders. Kang SL, Shaikh AG, Ghasia FF. Front Neurol. 2018; 9: 299. PMCID: PMC5964131.

A Dynamic circuit hypothesis for the pathogenesis of blepharospasm. Peterson DA, Sejnowski TJ. Front Comput Neurosci. 2017; 11: 11. PMCID: PMC5340098. [Review]

Acquired pendular nystagmus. Kang S, Shaikh AG. J Neurol Sci. 2017 Apr 15;375:8-17. doi: 10.1016/j.jns.2017.01.033. Epub 2017 Jan 10.

Alterations of resting-state fMRI measurements in individuals with cervical dystonia. Li Z, Prudente CN, Stilla R, Sathian K, Jinnah HA, Hu X. Hum Brain Mapp. 2017 Aug;38(8):4098-4108. doi: 10.1002/hbm.23651. Epub 2017 May 15.

Basic and translational neuro-ophthalmology of visually guided saccades: disorders of velocity. Puri S, Shaikh AG. Expert Rev Ophthalmol. 2017;12(6):457-473. doi: 10.1080/17469899.2017.1395695. Epub 2017 Nov 28.

Blepharospasm 40 years later. Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. Mov Disord. 2017 Apr;32(4):498-509. doi: 10.1002/mds.26934. Epub 2017 Feb 10.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia. Shakkottai VG, Batla A, Bhatia K, Dauer WT, Dresel C, Niethammer M, Eidelberg D, Raike RS, Smith Y, Jinnah HA, Hess EJ, Meunier S, Hallett M, Fremont R, Khodakhah K, LeDoux MS, Popa T, Gallea C, Lehericy S, Bostan AC, Strick PL. Cerebellum. 2017 Apr;16(2):577-594. doi: 10.1007/s12311-016-0825-6.

Deep brain stimulation for dystonia: a novel perspective on the value of genetic testing. Jinnah HA, Alterman R, Klein C, Krauss JK, Moro E, Vidailhet M, Raike R. J Neural Transm (Vienna). 2017 Apr;124(4):417-430. doi: 10.1007/s00702-016-1656-9. Epub 2017 Feb 3.

Diffusion-Weighted Magnetic Resonance Imaging in Acute Retinal Pathology. Alsinaidi O, Shaikh AG. Neuroophthalmology. 2017 Oct 13;42(3):191-193. doi: 10.1080/01658107.2017.1354385. eCollection 2018 Jun.

Dystonia treatment: patterns of medication use in an international cohort. Pirio Richardson S, Wegele A, Skipper B et al. Neurology. 2017; 88: 543-550. PMCID: PMCID: 5304465.

Fixational eye movements in Tourette syndrome. Shaikh AG, Finkelstein SR, Schuchard R, Ross G, Juncos JL. Neurol Sci. 2017 Nov;38(11):1977-1984. doi: 10.1007/s10072-017-3069-4. Epub 2017 Aug 16.

Fixational saccades are more disconjugate in adults than in children. Shaikh AG, Ghasia FF. PLoS One. 2017 Apr 13;12(4):e0175295. doi: 10.1371/journal.pone.0175295. eCollection 2017.

Increased blinking may be a precursor of blepharospasm: a longitudinal study. Conte A, Ferrazzano G, Defazio G et al. Mov Disord Clin Pract. 2017; 4: 733-736. PMCID: PMC5654574.

Motion Illusion-Evidence towards Human Vestibulo-Thalamic Projections. Shaikh AG, Straumann D, Palla A. Cerebellum. 2017 Jun;16(3):656-663. doi: 10.1007/s12311-017-0844-y.

Novel Eye Movement Disorders in Whipple's Disease-Staircase Horizontal Saccades, Gaze-Evoked Nystagmus, and Esotropia. Shaikh AG, Ghasia FF. Front Neurol. 2017 Jul 11;8:321. doi: 10.3389/fneur.2017.00321. eCollection 2017.

Physiology of midbrain head movement neurons in cervical dystonia. Sedov A, Popov V, Shabalov V, Raeva S, Jinnah HA, Shaikh AG. Mov Disord. 2017 Jun;32(6):904-912. doi: 10.1002/mds.26948. Epub 2017 Feb 20.

Psychiatric associations of adult-onset focal dystonia phenotypes. Berman BD, Junker J, Shelton E, Sillau SH, Jinnah HA, Perlmutter JS, Espay AJ, Jankovic J, Vidailhet M, Bonnet C, Ondo W, Malaty IA, Rodríguez R, McDonald WM, Marsh L, Zurowski M, Bäumer T, Brüggemann N. J Neurol Neurosurg Psychiatry. 2017 Jul;88(7):595-602. doi: 10.1136/jnnp-2016-315461. Epub 2017 Apr 24.

Reply: Contributions of visual and motor signals in cervical dystonia. Shaikh AG, Zee DS, Crawford JD et al. Brain. 2017; 140: e5. [Letter]

Research Priorities in Limb and Task-Specific Dystonias. Pirio Richardson S, Altenmüller E, Alter K, Alterman RL, Chen R, Frucht S, Furuya S, Jankovic J, Jinnah HA, Kimberley TJ, Lungu C, Perlmutter JS, Prudente CN, Hallett M. Front Neurol. 2017 May 3;8:170. doi: 10.3389/fneur.2017.00170. eCollection 2017.

Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and slow. Shaikh AG, Factor SA, Juncos J. Mov Disord Clin Pract. 2017 Sep-Oct;4(5):671-681. doi: 10.1002/mdc3.12491. Epub 2017 Aug 11.

The anatomical basis for dystonia: The motor network model. Jinnah HA, Neychev V, Hess EJ. Tremor Other Hyperkinet Mov (N Y). 2017; 7: 506. PMCID: PMC5673689. [Invited Review]

Using the shared genetics of dystonia and ataxia to unravel their pathogenesis. Nibbeling EA, Delnooz CC, de Koning TJ, Sinke RJ, Jinnah HA, Tijssen MA, Verbeek DS. Neurosci Biobehav Rev. 2017 Apr;75:22-39. doi: 10.1016/j.neubiorev.2017.01.033. Epub 2017 Jan 28.

"Complex" dystonia is not a category in the new 2013 consensus classification. Albanese A, Bhatia K, DeLong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Mink JW, Teller JK. Mov Disord. 2016 Nov;31(11):1758-1759. doi: 10.1002/mds.26764. Epub 2016 Sep 10.

Abnormal interhemispheric inhibition in musician's dystonia - Trait or state?. Bäumer T, Schmidt A, Heldmann M, Landwehr M, Simmer A, Tönniges D, Münte T, Lohmann K, Altenmüller E, Klein C, Münchau A. Parkinsonism Relat Disord. 2016 Apr;25:33-8. doi: 10.1016/j.parkreldis.2016.02.018. Epub 2016 Feb 20.

Blepharospasm in a multiplex African-American pedigree. Xiao J, Thompson MM, Vemula SR et al. J Neurol Sci. 2016; 362: 299-303. PMCID: PMC4779500.

Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes. Jinnah HA, Goodmann E, Rosen AR, Evatt M, Freeman A, Factor S. J Neurol. 2016 Jun;263(6):1188-94. doi: 10.1007/s00415-016-8136-x. Epub 2016 Apr 25.

Cervical dystonia: a neural integrator disorder. Shaikh AG, Zee DS, Crawford JD, Jinnah HA. Brain. 2016 Oct;139(Pt 10):2590-2599. doi: 10.1093/brain/aww141. Epub 2016 Jun 20.

Clinical and demographic characteristics related to onset site and spread of cervical dystonia. Norris SA, Jinnah HA, Espay AJ, Klein C, Brüggemann N, Barbano RL, Malaty IA, Rodriguez RL, Vidailhet M, Roze E, Reich SG, Berman BD, LeDoux MS, Richardson SP, Agarwal P, Mari Z, Ondo WG, Shih LC, Fox SH, Berardelli A, Testa CM, Cheng FC, Truong D, Nahab FB, Xie T, Hallett M, Rosen AR, Wright LJ, Perlmutter JS. Mov Disord. 2016 Dec;31(12):1874-1882. doi: 10.1002/mds.26817. Epub 2016 Oct 18.

Clinical and genetic features of cervical dystonia in a large multicenter cohort. LeDoux MS, Vemula SR, Xiao J, Thompson MM, Perlmutter JS, Wright LJ, Jinnah HA, Rosen AR, Hedera P, Comella CL, Weissbach A, Junker J, Jankovic J, Barbano RL, Reich SG, Rodriguez RL, Berman BD, Chouinard S, Severt L, Agarwal P, Stover NP. Neurol Genet. 2016 Apr 11;2(3):e69. doi: 10.1212/NXG.0000000000000069. eCollection 2016 Jun.

Clinimetric testing of the comprehensive cervical dystonia rating scale. Comella CL, Perlmutter JS, Jinnah HA, Waliczek TA, Rosen AR, Galpern WR, Adler CA, Barbano RL, Factor SA, Goetz CG, Jankovic J, Reich SG, Rodriguez RL, Severt WL, Zurowski M, Fox SH, Stebbins GT. Mov Disord. 2016 Apr;31(4):563-9. doi: 10.1002/mds.26534. Epub 2016 Mar 12.

Comparative effectiveness of propranolol and botulinum for the treatment of essential voice tremor. Justicz N, Hapner ER, Josephs JS, Boone BC, Jinnah HA, Johns MM 3rd. Laryngoscope. 2016 Jan;126(1):113-7. doi: 10.1002/lary.25485. Epub 2015 Jul 21.

Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?. Fraint A, Vittal P, Comella C. Ther Clin Risk Manag. 2016; 12: 147-54. PMCID: PMC4751901. [Review]

DYT1 dystonia increases risk taking in humans. Arkadir D, Radulescu A, Raymond D et al. eLife 2016;10.7554. PMCID: PMC4951192.

DYT6 Dystonia: A Neuropathological Study. Paudel R, Li A, Hardy J, Bhatia KP, Houlden H, Holton J. Neurodegener Dis. 2016;16(3-4):273-8. doi: 10.1159/000440863. Epub 2015 Nov 27.

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia. Bologna M, Paparella G, Fabbrini A, Leodori G, Rocchi L, Hallett M, Berardelli A. Clin Neurophysiol. 2016 Nov;127(11):3472-3479. doi: 10.1016/j.clinph.2016.09.008. Epub 2016 Sep 15.

Locus Pocus. Jinnah HA. Mov Disord. 2016 Nov;31(11):1759-1760. doi: 10.1002/mds.26765. Epub 2016 Aug 22.

Objective, computerized video-based rating of blepharospasm severity. Peterson DA, Littlewort GC, Bartlett MS, Macerollo A, Perlmutter JS, Jinnah HA, Hallett M, Sejnowski TJ. Peterson D, Littlewort G, Bartlett M et al. Objective, computerized, video-based rating of blepharospasm severity. Neurology. 2016; 87: 2146-2153. PMCID: PMC5109937.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

The role of polymyography in the treatment of cervical dystonia: the authors reply. Jinnah HA, Factor S. J Neurol. 2016 Aug;263(8):1665. doi: 10.1007/s00415-016-8222-0. Epub 2016 Jul 8.

Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism. Schottlaender LV, Polke JM, Ling H, MacDoanld ND, Tucci A, Nanji T, Pittman A, de Silva R, Holton JL, Revesz T, Sweeney MG, Singleton AB, Lees AJ, Bhatia KP, Houlden H. Neurobiol Aging. 2015 Feb;36(2):1221.e1-6. doi: 10.1016/j.neurobiolaging.2014.08.024. Epub 2014 Aug 27.

Central Nervous System Control of Voice and Swallowing. Ludlow CL. J Clin Neurophysiol. 2015 Aug;32(4):294-303. doi: 10.1097/WNP.0000000000000186.

Development and validation of a clinical scale for rating the severity of blepharospasm. Defazio G, Hallett M, Jinnah HA, Stebbins GT, Gigante AF, Ferrazzano G, Conte A, Fabbrini G, Berardelli A. Mov Disord. 2015 Apr;30(4):525-30. doi: 10.1002/mds.26156.

Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology. Comella CL, Fox SH, Bhatia KP, Perlmutter JS, Jinnah HA, Zurowski M, McDonald WM, Marsh L, Rosen AR, Waliczek T, Wright LJ, Galpern WR, Stebbins GT. Mov Disord Clin Pract. 2015 Jun;2(2):135-141. doi: 10.1002/mdc3.12131. Epub 2015 Apr 6.

Diagnosis and treatment of dystonia. Jinnah HA, Factor SA. Neurol Clin. 2015 Feb;33(1):77-100. doi: 10.1016/j.ncl.2014.09.002.

Diagnostic Delays in Spasmodic Dysphonia: A Call for Clinician Education. Creighton FX, Hapner E, Klein A, Rosen A, Jinnah HA, Johns MM. J Voice. 2015 Sep;29(5):592-4. doi: 10.1016/j.jvoice.2013.10.022. Epub 2015 Apr 11.

Dystonia: Five new things. Berman BD, Jinnah HA. Neurol Clin Pract. 2015 Jun;5(3):232-240. doi: 10.1212/CPJ.0000000000000128.

Laryngeal Reflexes: Physiology, Technique, and Clinical Use. Ludlow CL. J Clin Neurophysiol. 2015 Aug;32(4):284-93. doi: 10.1097/WNP.0000000000000187.

Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia. Kimberley TJ, Schmidt RL, Chen M et al. Front Hum Neurosci. 2015; 9: 385. PMCID: PMC4496570.

Neural Substrates for Head Movements in Humans: A Functional Magnetic Resonance Imaging Study. Prudente CN, Stilla R, Buetefisch CM, Singh S, Hess EJ, Hu X, Sathian K, Jinnah HA. J Neurosci. 2015 Jun 17;35(24):9163-72. doi: 10.1523/JNEUROSCI.0851-15.2015.

Ocular palatal tremor plus dystonia - new syndromic association. Shaikh AG, Ghasia FF, DeLong MR, Jinnah HA, Freeman A, Factor SA. Mov Disord Clin Pract. 2015 Sep 1;2(3):267-270. doi: 10.1002/mdc3.12193. Epub 2015 Jun 17.

Oscillatory head movements in cervical dystonia: Dystonia, tremor, or both?. Shaikh AG, Zee DS, Jinnah HA. Mov Disord. 2015 May;30(6):834-42. doi: 10.1002/mds.26231. Epub 2015 Apr 16.

Recent developments in dystonia. Jinnah HA, Teller JK, Galpern WR. Curr Opin Neurol. 2015 Aug;28(4):400-5. doi: 10.1097/WCO.0000000000000213.

Repetitive transcranial magnetic stimulation in cervical dystonia:  effect of site and repetition in a randomized pilot trial. Pirio Richardson S, Tinaz S, Chen R. PLoS One. 2015; 10: e0124937. PMCID: PMC4414555.

Secured web-based video repository for multicenter studies. Yan L, Hicks M, Winslow K, Comella C, Ludlow C, Jinnah HA, Rosen AR, Wright L, Galpern WR, Perlmutter JS. Parkinsonism Relat Disord. 2015 Apr;21(4):366-71. doi: 10.1016/j.parkreldis.2015.01.011. Epub 2015 Jan 20.

Short- and long-term outcome of chronic pallidal neurostimulation in monogenic isolated dystonia. Brüggemann N, Kühn A, Schneider SA, Kamm C, Wolters A, Krause P, Moro E, Steigerwald F, Wittstock M, Tronnier V, Lozano AM, Hamani C, Poon YY, Zittel S, Wächter T, Deuschl G, Krüger R, Kupsch A, Münchau A, Lohmann K, Volkmann J, Klein C. Neurology. 2015 Mar 3;84(9):895-903. doi: 10.1212/WNL.0000000000001312. Epub 2015 Feb 4.

Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation. Shaikh AG, Mewes K, DeLong MR, Gross RE, Triche SD, Jinnah HA, Boulis N, Willie JT, Freeman A, Alexander GE, Aia P, Butefisch CM, Esper CD, Factor SA. Parkinsonism Relat Disord. 2015 Feb;21(2):116-9. doi: 10.1016/j.parkreldis.2014.11.013. Epub 2014 Nov 20.

The neurobiology of dystonia. Jinnah HA, Prudente CN, Rose SJ et al. In Neurobiology of Disease, 2nd Ed, 2015. [Chapter]

The role of dopamine and dopaminergic pathways in dystonia: insights from neuroimaging. Karimi M, Perlmutter JS. Tremor Other Hyperkinet Mov (N Y). 2015 Jan 29;5:280. doi: 10.7916/D8J101XV. eCollection 2015.

When brawn benefits brain: physical activity and Parkinson's disease risk. Tanner CM, Comella CL. Brain. 2015 Feb;138(Pt 2):238-9. doi: 10.1093/brain/awu351.

Why are voluntary head movements in cervical dystonia slow?. Shaikh AG, Wong A, Zee DS, Jinnah HA. Parkinsonism Relat Disord. 2015 Jun;21(6):561-6. doi: 10.1016/j.parkreldis.2015.03.005. Epub 2015 Mar 14.

A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia. Vemula SR, Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Hedera P, Truong DD, Blitzer A, Rudzińska M, Momčilović D, Jinnah HA, Frei K, Pfeiffer RF, LeDoux MS. Mol Genet Genomic Med. 2014 May;2(3):261-72. doi: 10.1002/mgg3.67. Epub 2014 Feb 11.

Activation of upper airway muscles during breathing and swallowing. Fregosi RF, Ludlow CL. J Appl Physiol (1985). 2014 Feb 1;116(3):291-301. doi: 10.1152/japplphysiol.00670.2013. Epub 2013 Oct 3.

Alleviating manoeuvres (sensory tricks) in cervical dystonia. Patel N, Hanfelt J, Marsh L, Jankovic J; members of the Dystonia Coalition. J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):882-4. doi: 10.1136/jnnp-2013-307316. Epub 2014 May 14.

An ¹⁸F-FDG PET study of cervical muscle in parkinsonian anterocollis. Revuelta GJ, Montilla J, Benatar M, Freeman A, Wichmann T, Jinnah HA, Delong MR, Factor SA. J Neurol Sci. 2014 May 15;340(1-2):174-7. doi: 10.1016/j.jns.2014.03.023. Epub 2014 Mar 18.

Closed-loop brain-machine-body interfaces for noninvasive rehabilitation of movement disorders. Broccard FD, Mullen T, Chi YM, Peterson D, Iversen JR, Arnold M, Kreutz-Delgado K, Jung TP, Makeig S, Poizner H, Sejnowski T, Cauwenberghs G. Ann Biomed Eng. 2014 Aug;42(8):1573-93. doi: 10.1007/s10439-014-1032-6. Epub 2014 May 15.

Designing clinical trials for dystonia. Galpern WR, Coffey CS, Albanese A, Cheung K, Comella CL, Ecklund DJ, Fahn S, Jankovic J, Kieburtz K, Lang AE, McDermott MP, Shefner JM, Teller JK, Thompson JL, Yeatts SD, Jinnah HA. Neurotherapeutics. 2014 Jan;11(1):117-27. doi: 10.1007/s13311-013-0221-6.

Dystonia as a network disorder: what is the role of the cerebellum?. Prudente CN, Hess EJ, Jinnah HA. Neuroscience. 2014 Feb 28;260:23-35. doi: 10.1016/j.neuroscience.2013.11.062. Epub 2013 Dec 11.

Globus pallidus deep brain stimulation for adult-onset axial dystonia. Shaikh AG, Mewes K, Jinnah HA, DeLong MR, Gross RE, Triche S, Freeman A, Factor SA. Parkinsonism Relat Disord. 2014 Nov;20(11):1279-82. doi: 10.1016/j.parkreldis.2014.09.005. Epub 2014 Sep 16.

Loss of dopamine phenotype among midbrain neurons in Lesch-Nyhan disease. Göttle M, Prudente CN, Fu R, Sutcliffe D, Pang H, Cooper D, Veledar E, Glass JD, Gearing M, Visser JE, Jinnah HA. Ann Neurol. 2014 Jul;76(1):95-107. doi: 10.1002/ana.24191. Epub 2014 Jun 20.

Neuroimaging biomarkers for Parkinson disease: facts and fantasy. Perlmutter JS, Norris SA. Ann Neurol. 2014 Dec;76(6):769-83. doi: 10.1002/ana.24291. Epub 2014 Nov 7.

Neuropathological features of genetically confirmed DYT1 dystonia: investigating disease-specific inclusions. Paudel R, Kiely A, Li A, Lashley T, Bandopadhyay R, Hardy J, Jinnah HA, Bhatia K, Houlden H, Holton JL. Acta Neuropathol Commun. 2014 Nov 18;2:159. doi: 10.1186/s40478-014-0159-x.

New concepts for dystonia. Jinnah HA, Albanese A. Jinnah HA, Albanese A. New concepts for dystonia. Moving Along: The Official Newsletter of the International Parkinson and Movement Disorder Society. 2014; 18: 6-7. [Feature article]

Pathogenic variants in TUBB4A are not found in primary dystonia. Vemula SR, Xiao J, Bastian RW, Momčilović D, Blitzer A, LeDoux MS. Neurology. 2014 Apr 8;82(14):1227-30. doi: 10.1212/WNL.0000000000000294. Epub 2014 Mar 5.

Recent advances in the genetics of dystonia. Xiao J, Vemula SR, LeDoux MS. Curr Neurol Neurosci Rep. 2014 Aug;14(8):462. doi: 10.1007/s11910-014-0462-8.

Reply: dystonia after severe head injuries. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Mov Disord. 2014 Apr;29(4):578-9. doi: 10.1002/mds.25861. Epub 2014 Mar 3.

Smoking and Parkinson disease: where there is smoke there may not be fire. Hershey LA, Perlmutter JS. Neurology. 2014 Oct 14;83(16):1392-3. doi: 10.1212/WNL.0000000000000896. Epub 2014 Sep 12.

The New Classification System for the Dystonias: Why Was it Needed and How was it Developed?. Jinnah HA, Albanese A. Mov Disord Clin Pract. 2014 Dec 1;1(4):280-284. doi: 10.1002/mdc3.12100.

Treatment of myoclonus-dystonia syndrome with tetrabenazine. Luciano AY, Jinnah HA, Pfeiffer RF, Truong DD, Nance MA, LeDoux MS. Parkinsonism Relat Disord. 2014 Dec;20(12):1423-6. doi: 10.1016/j.parkreldis.2014.09.029. Epub 2014 Oct 5.

Treatment of restless legs syndrome. Comella CL. Neurotherapeutics. 2014 Jan;11(1):177-87. doi: 10.1007/s13311-013-0247-9.

Assessment of patients with isolated or combined dystonia: an update on dystonia syndromes. Fung VS, Jinnah HA, Bhatia K, Vidailhet M. Mov Disord. 2013 Jun 15;28(7):889-98. doi: 10.1002/mds.25549.

Cerebellar processing of sensory inputs primes motor cortex plasticity. Popa T, Velayudhan B, Hubsch C, Pradeep S, Roze E, Vidailhet M, Meunier S, Kishore A. Cereb Cortex. 2013 Feb;23(2):305-14. doi: 10.1093/cercor/bhs016. Epub 2012 Feb 20.

Defective cerebellar control of cortical plasticity in writer's cramp. Hubsch C, Roze E, Popa T, Russo M, Balachandran A, Pradeep S, Mueller F, Brochard V, Quartarone A, Degos B, Vidailhet M, Kishore A, Meunier S. Brain. 2013 Jul;136(Pt 7):2050-62. doi: 10.1093/brain/awt147.

Depression and Parkinson's disease: current knowledge. Marsh L. Curr Neurol Neurosci Rep. 2013 Dec;13(12):409. doi: 10.1007/s11910-013-0409-5.

Development and validation of a clinical guideline for diagnosing blepharospasm. Defazio G, Hallett M, Jinnah HA, Berardelli A. Neurology. 2013 Jul 16;81(3):236-40. doi: 10.1212/WNL.0b013e31829bfdf6. Epub 2013 Jun 14.

Dystonia rating scales: critique and recommendations. Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Mov Disord. 2013 Jun 15;28(7):874-83. doi: 10.1002/mds.25579.

Dystonia, facial dysmorphism, intellectual disability and breast cancer associated with a chromosome 13q34 duplication and overexpression of TFDP1: case report. Moscovich M, LeDoux MS, Xiao J, Rampon GL, Vemula SR, Rodriguez RL, Foote KD, Okun MS. BMC Med Genet. 2013 Jul 13;14:70. doi: 10.1186/1471-2350-14-70.

Genetics of dystonia: What's known? What's new? What's next?. Lohmann K, Klein C. Mov Disord. 2013; 28: 899-905. [Invited Review]

How long does it take to diagnose cervical dystonia?. Tiderington E, Goodman EM, Rosen AR, Hapner ER, Johns MM 3rd, Evatt ML, Freeman A, Factor S, Jinnah HA. J Neurol Sci. 2013 Dec 15;335(1-2):72-4. doi: 10.1016/j.jns.2013.08.028. Epub 2013 Aug 30.

Keeping your head on target. Shaikh AG, Wong AL, Zee DS, Jinnah HA. J Neurosci. 2013 Jul 3;33(27):11281-95. doi: 10.1523/JNEUROSCI.3415-12.2013.

Neuropathology of cervical dystonia. Prudente CN, Pardo CA, Xiao J, Hanfelt J, Hess EJ, Ledoux MS, Jinnah HA. Exp Neurol. 2013 Mar;241:95-104. doi: 10.1016/j.expneurol.2012.11.019. Epub 2012 Nov 27.

Phenomenology and classification of dystonia: a consensus update. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.

Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase. Ceballos-Picot I, Augé F, Fu R, Olivier-Bandini A, Cahu J, Chabrol B, Aral B, de Martinville B, Lecain JP, Jinnah HA. Mol Genet Metab. 2013 Nov;110(3):268-74. doi: 10.1016/j.ymgme.2013.08.016. Epub 2013 Sep 8.

Psychiatric comorbidities in dystonia: emerging concepts. Zurowski M, McDonald WM, Fox S, Marsh L. Mov Disord. 2013 Jun 15;28(7):914-20. doi: 10.1002/mds.25501.

Rating scales for musician's dystonia: the state of the art. Peterson DA, Berque P, Jabusch HC, Altenmüller E, Frucht SJ. Neurology. 2013 Aug 6;81(6):589-98. doi: 10.1212/WNL.0b013e31829e6f72. Epub 2013 Jul 24.

Secondary blepharospasm associated with structural lesions of the brain. Khooshnoodi MA, Factor SA, Jinnah HA. J Neurol Sci. 2013 Aug 15;331(1-2):98-101. doi: 10.1016/j.jns.2013.05.022. Epub 2013 Jun 6.

Special concerns in defining, studying, and treating dystonia in children. Mink JW. Mov Disord. 2013 Jun 15;28(7):921-5. doi: 10.1002/mds.25548.

The dystonias: past, present, and future. Jinnah HA, Delong MR, Hallett M. Mov Disord. 2013 Jun 15;28(7):849-50. doi: 10.1002/mds.25564.

The focal dystonias: current views and challenges for future research. Jinnah HA, Berardelli A, Comella C, Defazio G, Delong MR, Factor S, Galpern WR, Hallett M, Ludlow CL, Perlmutter JS, Rosen AR; Dystonia Coalition Investigators. Mov Disord. 2013 Jun 15;28(7):926-43. doi: 10.1002/mds.25567.

Translation of Oppenheim's 1911 paper on dystonia. Klein C, Fahn S. Mov Disord. 2013; 28: 851-862. PMCID: In Progress. [Translation from German]

Clinical subtypes of anterocollis in parkinsonian syndromes. Revuelta GJ, Benatar M, Freeman A, Wichmann T, Jinnah HA, DeLong MR, Factor SA. J Neurol Sci. 2012 Apr 15;315(1-2):100-3. doi: 10.1016/j.jns.2011.11.017. Epub 2011 Nov 30.

Coprevalence of anxiety and depression with spasmodic dysphonia: a case-control study. White LJ, Hapner ER, Klein AM, Delgaudio JM, Hanfelt JJ, Jinnah HA, Johns MM 3rd. J Voice. 2012 Sep;26(5):667.e1-6. doi: 10.1016/j.jvoice.2011.08.011. Epub 2011 Dec 29.

Dystonia: phenomenology. LeDoux MS. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1(Suppl 1):S162-4. doi: 10.1016/S1353-8020(11)70050-5.

Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases. LeDoux MS, Xiao J, Rudzińska M, Bastian RW, Wszolek ZK, Van Gerpen JA, Puschmann A, Momčilović D, Vemula SR, Zhao Y. Parkinsonism Relat Disord. 2012 Jun;18(5):414-25. doi: 10.1016/j.parkreldis.2012.02.001. Epub 2012 Feb 28.

Mutations in CIZ1 cause adult onset primary cervical dystonia. Xiao J, Uitti RJ, Zhao Y, Vemula SR, Perlmutter JS, Wszolek ZK, Maraganore DM, Auburger G, Leube B, Lehnhoff K, LeDoux MS. Ann Neurol. 2012 Apr;71(4):458-69. doi: 10.1002/ana.23547. Epub 2012 Mar 23.

Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia. Hedera P, Xiao J, Puschmann A, Momčilović D, Wu SW, LeDoux MS. BMC Neurol. 2012 Sep 18;12:93. doi: 10.1186/1471-2377-12-93.

Oromandibular and lingual dystonia associated with spinocerebellar ataxia type 8. Ushe M, Perlmutter JS. Mov Disord. 2012 Dec;27(14):1741-2. doi: 10.1002/mds.25295.

Prevalence, predictors, and perceived effectiveness of complementary, alternative and integrative medicine in adult-onset primary dystonia. Fleming BM, Schwab EL, Nouer SS, Wan JY, LeDoux MS. Parkinsonism Relat Disord. 2012 Sep;18(8):936-40. doi: 10.1016/j.parkreldis.2012.04.027. Epub 2012 May 25.

The genetics of dystonias. LeDoux MS. Adv Genet. 2012;79:35-85. doi: 10.1016/B978-0-12-394395-8.00002-5.

An African-American family with dystonia. Puschmann A, Xiao J, Bastian RW, Searcy JA, LeDoux MS, Wszolek ZK. Parkinsonism Relat Disord. 2011 Aug;17(7):547-50. doi: 10.1016/j.parkreldis.2011.04.019. Epub 2011 May 20.

Animal models of dystonia: Lessons from a mutant rat. LeDoux MS. Neurobiol Dis. 2011 May;42(2):152-61. doi: 10.1016/j.nbd.2010.11.006. Epub 2010 Nov 21.

Convergent mechanisms in etiologically-diverse dystonias. Thompson VB, Jinnah HA, Hess EJ. Expert Opin Ther Targets. 2011 Dec;15(12):1387-403. doi: 10.1517/14728222.2011.641533. Epub 2011 Dec 3.

Coprevalence of tremor with spasmodic dysphonia: a case-control study. White LJ, Klein AM, Hapner ER, Delgaudio JM, Hanfelt JJ, Jinnah HA, Johns MM 3rd. Laryngoscope. 2011 Aug;121(8):1752-5. doi: 10.1002/lary.21872.

Extreme task specificity in writer's cramp. Shamim EA, Chu J, Scheider LH, Savitt J, Jinnah HA, Hallett M. Mov Disord. 2011 Sep;26(11):2107-9. doi: 10.1002/mds.23827. Epub 2011 Jun 28.

In the wink of an eye: nature and nurture in blepharospasm. Jinnah HA, Hallett M. Neurology. 2011 Aug 16;77(7):616-7. doi: 10.1212/WNL.0b013e3182299f84. Epub 2011 Jul 20.

Needles in haystacks: the challenges of rare diseases. Jinnah HA. Dev Med Child Neurol. 2011 Jan;53(1):6-7. doi: 10.1111/j.1469-8749.2010.03791.x.

Spasmodic dysphonia: a laryngeal control disorder specific to speech. Ludlow CL. J Neurosci. 2011 Jan 19;31(3):793-7. doi: 10.1523/JNEUROSCI.2758-10.2011.

The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia. Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Blitzer A, Rudzińska M, Pfeiffer RF, Le C, LeDoux MS. Mov Disord. 2011 Feb 15;26(3):549-52. doi: 10.1002/mds.23551. Epub 2011 Mar 2.

The functional neuroanatomy of dystonia. Neychev VK, Gross RE, Lehéricy S, Hess EJ, Jinnah HA. Neurobiol Dis. 2011 May;42(2):185-201. doi: 10.1016/j.nbd.2011.01.026. Epub 2011 Feb 12.

Neuronal voltage-gated calcium channels: brief overview of their function and clinical implications in neurology. Hess EJ, Jen JC, Jinnah HA, Benarroch EE. Neurology. 2010 Sep 7;75(10):937; author reply 937-8. doi: 10.1212/WNL.0b013e3181eee9e8.

Novel THAP1 sequence variants in primary dystonia. Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Dev Batish S, Blitzer A, Pfeiffer RF, Gong S, LeDoux MS. Neurology. 2010 Jan 19;74(3):229-38. doi: 10.1212/WNL.0b013e3181ca00ca.

Treatment strategies for dystonia. Cloud LJ, Jinnah HA. Expert Opin Pharmacother. 2010 Jan;11(1):5-15. doi: 10.1517/14656560903426171.

Rodent models of dystonia. Hess EJ, Jinnah HA. In Animal models for movement disorders, LeDoux MS, Ed. Elsevier Academic Press, Amsterdam, 2005. [Book chapter]

Dysregulated proteome and N-glycoproteome in ALG1-deficient fibroblasts. Budhraja R, Joshi N, Radenkovic S, Kozicz T, Morava E, Pandey A. Proteomics. 2024 Mar 12:e2400012. doi: 10.1002/pmic.202400012. Epub ahead of print. PMID: 38470198.

ALG1-congenital disorder of glycosylation (ALG1-CDG) is an inherited disorder caused by variants in the ALG1 gene. These variants affect N-glycosylation, which is the body’s process of creating, changing, and attaching sugar blocks to proteins and lipids. However, not much is known about how these variants affect the cellular proteome (proteins expressed in cells) and the process of glycosylation.

In this study, researchers explored proteomics and N-glycoproteomics in ALG1-CDG. The team studied fibroblasts (connective tissue cells) from three individuals with different ALG1 variants.

Results revealed altered protein levels and a reduction of mature forms of glycopeptides. Authors note that these results can help us understand the biology and molecular mechanisms of ALG1-CDG, differentiate CDG types, and identify potential biomarkers.

Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models. Radenkovic S, Budhraja R, Klein-Gunnewiek T, King AT, Bhatia TN, Ligezka AN, Driesen K, Shah R, Ghesquière B, Pandey A, Kasri NN, Sloan SA, Morava E, Kozicz T. Cell Rep. 2024 Mar 1;43(3):113883. doi: 10.1016/j.celrep.2024.113883. Epub ahead of print. PMID: 38430517.

PMM2-congenital disorder of glycosylation (PMM2-CDG) is an inherited condition caused by mutations in the PMM2 gene. Most individuals with PMM2-CDG experience neurological symptoms. However, not much is known about the specific brain-related changes caused by PMM2 deficiency.

In this study, researchers explored the neurological characteristics of PMM2-CDG using human in vitro neural models. The team created human induced pluripotent stem cell (hiPSC)-derived neural models to observe changes in neural function and metabolic dynamics.

Results revealed disrupted functioning of PMM2-deficient neuronal networks, as well as widespread changes in metabolite composition, RNA expression, protein abundance, and protein glycosylation. Authors note that these findings introduce potentially critical factors contributing to the early neural issues in patients with PMM2-CDG, paving the way for exploring innovative treatment approaches.

AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase 1 deficiency (PGM1-CDG). Balakrishnan B, Altassan R, Budhraja R, Liou W, Lupo A, Bryant S, Mankouski A, Radenkovic S, Preston GJ, Pandey A, Boudina S, Kozicz T, Morava-Kozicz E, Lai K. Transl Res. 2023 Jul;257:1-14. doi: 10.1016/j.trsl.2023.01.004. Epub 2023 Jan 26.

Beyond genetics: Deciphering the impact of missense variants in CAD deficiency. Del Caño-Ochoa F, Ng BG, Rubio-Del-Campo A, Mahajan S, Wilson MP, Vilar M, Rymen D, Sánchez-Pintos P, Kenny J, Martos ML, Campos T, Wortmann SB, Freeze HH, Ramón-Maiques S. J Inherit Metab Dis. 2023 Aug 4. doi: 10.1002/jimd.12667. Epub ahead of print. PMID: 37540500

CAD deficiency is a rare congenital disorder of glycosylation characterized by epileptic encephalopathy (disease affecting the brain). Because symptoms are non-specific, there is no biomarker, and the CAD protein has over 1,000 known variants, CAD deficiency is difficult to diagnose.

In this study, researchers aimed to improve diagnosis of CAD deficiency. The team assessed the disease-causing ability of both previously reported and unreported CAD variants. Additionally, researchers studied the impact of disease-causing variants at the protein level.

Authors note that combining these functional and protein structural analysis methods can help refine clinical diagnostic workflow for CAD variants.

Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation. De Graef D, Ligezka AN, Rezents J, Mazza GL, Preston G, Schwartz K, Krzysciak W, Lam C, Edmondson AC, Johnsen C, Kozicz T, Morava E. Mol Genet Metab. 2023 Jun;139(2):107606. doi: 10.1016/j.ymgme.2023.107606. Epub 2023 May 9.

Combined PMM2-CDG and hereditary fructose intolerance in a patient with mild clinical presentation. Hong X, Edmondson AC, Strong A, Pomerantz D, Michl E, Berry G, He M. Mol Genet Metab. 2023 Aug 9;140(3):107682. doi: 10.1016/j.ymgme.2023.107682. Online ahead of print.

Congenital disorders of glycosylation: narration of a story through its patents. Monticelli M, D'Onofrio T, Jaeken J, Morava E, Andreotti G, Cubellis MV. Orphanet J Rare Dis. 2023 Aug 29;18(1):247. doi: 10.1186/s13023-023-02852-w.

Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases. Altassan R, Allers MM, De Graef D, Shah R, de Vries M, Larson A, Glamuzina E, Morava E. Mol Genet Metab. 2023 Nov;140(3):107688. doi: 10.1016/j.ymgme.2023.107688. Epub 2023 Aug 23.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. Alharbi H, Daniel EJP, Thies J, Chang I, Goldner DL, Ng BG, Witters P, Aqul A, Velez-Bartolomei F, Enns GM, Hsu E, Kichula E, Lee E, Lourenco C, Poskanzer SA, Rasmussen S, Saarela K, Wang YM, Raymond KM, Schultz MJ, Freeze HH, Lam C, Edmondson AC, He M. J Inherit Metab Dis. 2023 Mar;46(2):300-312. doi: 10.1002/jimd.12589. Epub 2023 Jan 29.

Interplay of Impaired Cellular Bioenergetics and Autophagy in PMM2-CDG. Ligezka AN, Budhraja R, Nishiyama Y, Fiesel FC, Preston G, Edmondson A, Ranatunga W, Van Hove JLK, Watzlawik JO, Springer W, Pandey A, Morava E, Kozicz T. Genes (Basel). 2023 Aug 4;14(8):1585. doi: 10.3390/genes14081585. PMID: 37628636; PMCID: PMC10454768

PMM2-CDG is a type of congenital disorder of glycosylation caused by mutations in the PMM2 gene. Some types of CDG are associated with dysfunction of the mitochondria, which generate energy to power cells. However, not much is known about cellular bioenergetics (how cells transform energy) in PMM2-CDG. 

In this study, researchers evaluated mitochondrial function and autophagy (the process of breaking down cellular contents) in PMM2-CDG. The team evaluated fibroblasts (skin cell-derived connective tissue cells) with different genotypes from a natural history study of individuals with PMM2-CDG. 

Results reveal secondary mitochondrial dysfunction in PMM2-CDG, as well as altered autophagy, which may act as a marker of disease severity. Authors note that manipulating these processes could offer therapeutic benefits when combined with existing treatments for PMM2-CDG. 

Liver transplantation recovers hepatic N-glycosylation with persistent IgG glycosylation abnormalities: Three-year follow-up in a patient with phosphomannomutase-2-congenital disorder of glycosylation. Tahata S, Weckwerth J, Ligezka A, He M, Lee HE, Heimbach J, Ibrahim SH, Kozicz T, Furuya K, Morava E. Mol Genet Metab. 2023 Apr;138(4):107559. doi: 10.1016/j.ymgme.2023.107559. Epub 2023 Mar 17.

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. Shah R, Johnsen C, Pletcher BA, Edmondson AC, Kozicz T, Morava E. Am J Med Genet A. 2023 Jun;191(6):1626-1631. doi: 10.1002/ajmg.a.63179. Epub 2023 Mar 17.

Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions. Muthusamy K, Perez-Ortiz JM, Ligezka AN, Altassan R, Johnsen C, Schultz MJ, Patterson MC, Morava E. Genet Med. 2023 Nov 10;26(2):101027. doi: 10.1016/j.gim.2023.101027. Online ahead of print.

Pathogenic DDOST Variant Is Associated with Humoral Immune Deficiency. Sitek A, Ligezka A, Budhraja R, Morava E, Chiarella SE. J Clin Immunol. 2023 May;43(4):692-694. doi: 10.1007/s10875-023-01429-3. Epub 2023 Jan 12.

Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis. Wang R, Helbig I, Edmondson AC, Lin L, Xing Y. Brief Bioinform. 2023 Sep 20;24(5):bbad284. doi: 10.1093/bib/bbad284. PMID: 37580177; PMCID: PMC10516351

Many rare diseases are caused by genomic variants that affect the process of pre-messenger RNA splicing and its regulation. However, these splice-altering variants are often overlooked by common workflows for genetic diagnosis and clinical variant interpretation.

In this review, researchers summarized recent developments and challenges in using RNA sequencing technologies to investigate rare diseases. Discussion included the use of new computational splicing prediction tools to reveal splice-altering variants.

Authors predict that continuous improvements to sequencing technologies and predictive modeling will expand our understanding of splicing regulation and improve diagnoses for rare disease patients.

The role of PGM1isoform 2 in PGM1-CDG: One step closer to genotype-phenotype correlation?. Radenkovic S, Laerdahl JK, Backe PH, Morava E. J Inherit Metab Dis. 2023 Mar;46(2):159-160. doi: 10.1002/jimd.12601.

Tracer metabolomics reveals the role of aldose reductase in glycosylation. Radenkovic S, Ligezka AN, Mokashi SS, Driesen K, Dukes-Rimsky L, Preston G, Owuocha LF, Sabbagh L, Mousa J, Lam C, Edmondson A, Larson A, Schultz M, Vermeersch P, Cassiman D, Witters P, Beamer LJ, Kozicz T, Flanagan-Steet H, Ghesquière B, Morava E. Cell Rep Med. 2023 Jun 20;4(6):101056. doi: 10.1016/j.xcrm.2023.101056. Epub 2023 May 30.

A 6-Month-Old Infant with Severe Failure to Thrive during COVID-19 Pandemic. Hong X, Alharbi H, Albokhari D, Edmondson AC, He M. Clin Chem. 2022 Jul 3;68(7):987-989. doi: 10.1093/clinchem/hvac012.

A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants. Geiculescu I, Dranove J, Cosper G, Edmondson AC, Morava-Kozicz E, Carter LB. Am J Med Genet A. 2022 Jun 4. doi: 10.1002/ajmg.a.62859. Epub ahead of print. PMID: 35665995.

Achalasia is a disorder of the esophagus, the tube that carries food from the mouth to the stomach. It is characterized by enlargement of the esophagus, impaired ability of the esophagus to push food down toward the stomach (peristalsis), and failure of the ring-shaped muscle at the bottom of the esophagus (the lower esophageal sphincter) to relax. Because achalasia is rare in the pediatric population, clinicians should consider associated genetic disorders. This includes GMPPA-congenital disorder of glycosylation (CDG), a rare type of CDG that is caused by variants in the GMPPA gene. In this study, researchers describe a 9-month-old female with achalasia and alacrima (reduced or absent ability to produce tears). The patient was found to have two novel compound heterozygous variants in the GMPPA gene that are associated with GMPPA-CDG. Authors provide a brief review of GMPPA-CDG, including management of this condition.

ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines. Albokhari D, Ng BG, Guberinic A, Daniel EJP, Engelhardt NM, Barone R, Fiumara A, Garavelli L, Trimarchi G, Wolfe L, Raymond KM, Morava E, He M, Freeze HH, Lam C, Edmondson AC. J Inherit Metab Dis. 2022 Jun 18. doi: 10.1002/jimd.12527. Epub ahead of print. PMID: 35716054.

ALG8-congenital disorder of glycosylation (ALG8-CDG) is a rare, inherited disorder that affects multiple systems in the body. Patients with ALG8-CDG commonly present with decreased muscle tone, intestinal problems, and liver problems. In this study, researchers describe seven new individuals with ALG8-CDG, bringing the total to 26 individuals reported in medical literature. The team diagnosed these patients based on biochemical and molecular testing, identifying nine novel variants in ALG8. The cohort also includes the two oldest patients reported to date. This study expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder, and other neuropsychiatric symptoms. Researchers also expand the clinical features in a variety of organ systems. To improve clinical management, authors suggest a comprehensive evaluation and monitoring strategy.

CDG or not CDG. Freeze HH, Jaeken J, Matthijs G. J Inherit Metab Dis. 2022 May;45(3):383-385. doi: 10.1002/jimd.12498. Epub 2022 Apr 1. PMID: 35338706; PMCID: PMC9121739.

In this letter to the editor, an expert team of authors explores a consensus on which genetic conditions should be identified as congenital disorders of glycosylation (CDG). “They are aiming to be inclusive; CDG should be used as the correct nomenclature in any disorders where the synthesis of glycans, glycoproteins, or glycolipids—including oligosaccharide transfer, glycan maturation, or trafficking—is affected,” says Eva Morava-Kozicz, MD, PhD, principal investigator of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC). “This is demonstrated by abnormal glycosylation in functional studies, and should be called a CDG.”

Chemical Therapies for Congenital Disorders of Glycosylation. Sosicka P, Ng BG, Freeze HH. ACS Chem Biol. 2022 Nov 18;17(11):2962-2971. doi: 10.1021/acschembio.1c00601. Epub 2021 Nov 17.

Clinical and molecular characterization of a third patient with a milder and a predominantly movement disorder phenotype. Elsharkawi I, Wongkittichote P, Daniel EJP, Starosta RT, Ueda K, Ng BG, Freeze HH, He M, Shinawi M. DDOST-CDG. J Inherit Metab Dis. 2022 Oct 10. doi: 10.1002/jimd.12565. Epub ahead of print. PMID: 36214423.

DDOST-CDG is an ultra-rare type of congenital disorder of glycosylation (CDG) that is caused by mutations in the gene DDOST. The metabolic disorder was previously reported in just two patients, whose clinical features included severe developmental delay, failure to thrive, and hypotonia (low muscle tone). Both patients also had abnormal transferrin glycosylation. In this study, researchers describe a new patient with DDOST-CDG. The 18-year-old male presented with moderate developmental delay, progressive opsoclonus (involuntary, rapid eye movements), myoclonus (involuntary, sudden muscle spasms), ataxia (impaired balance or coordination), tremor, and dystonia (involuntary muscle contractions that cause repetitive or twisting movements). The team performed several tests, including biochemical studies, exome sequencing, plasma N-glycan profiling, and western blot analysis, to learn more about the patient’s clinical features. Authors state that these insights—including new findings on the clinical variability, phenotypes, and genotypes of DDOST-CDG—are essential for diagnosing and managing patients with DDOST-CDG.

Clinical, biochemical and genetic characteristics of MOGS-CDG: a rare congenital disorder of glycosylation. Shimada S, Ng BG, White AL, Nickander KK, Turgeon C, Liedtke KL, Lam CT, Font-Montgomery E, Lourenco CM, He M, Peck DS, Umana LA, Uhles CL, Haynes D, Wheeler PG, Bamshad MJ, Nickerson DA, Cushing T, Gates R, Gomez-Ospina N, Byers HM; UW Center for Mendelian Genomics; Scalco FB, Martinez NN, Sachdev R, Smith L, Poduri A, Malone S, Harris RV, Scheffer IE, Rosenzweig SD, Adams DR, Gahl WA, Malicdan MCV, Raymond KM, Freeze HH, Wolfe LA. J Med Genet. 2022 Jul 5:jmedgenet-2021-108177. doi: 10.1136/jmedgenet-2021-108177. Online ahead of print.

Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1-congenital disorder of glycosylation) and response to l-fucose therapy: Insights from two new families and review of the literature. Tahata S, Raymond K, Quade M, Barnes S, Boyer S, League S, Kumanovics A, Abraham R, Jacob E, Menon P, Morava E. Am J Med Genet A. 2022 Mar 26. doi: 10.1002/ajmg.a.62737. Epub ahead of print. PMID: 35338746.

Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. Among a subset of patients with a milder presentation, descriptions have also included short stature and developmental delay with minimal immune and hematologic (relating to blood) features. While some patients with LAD II benefit from oral fucose therapy, this has not yet been studied in patients with milder disease. In this study, researchers describe three new patients from two separate families with the milder variant of LAD II and review the published literature. After 27 months of oral fucose supplementation, one patient showed improvements in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins. Authors note that these patients support classification of this disorder into distinct subtypes—a classical severe and an attenuated variant—and provide preliminary evidence of benefit of fucose therapy in the latter group.

Expanding the phenotypic spectrum of ARCN1-related syndrome. Ritter AL, Gold J, Hayashi H, Ackermann AM, Hanke S, Skraban C, Cuddapah S, Bhoj E, Li D, Kuroda Y, Wen J, Takeda R, Bibb A, El Chehadeh S, Piton A, Ohl J, Kukolich MK, Nagasaki K, Kato K, Ogi T, Bhatti T, Russo P, Krock B, Murrell JR, Sullivan JA, Shashi V, Stong N, Hakonarson H, Sawano K, Torti E, Willaert R, Si Y, Wilcox WR, Wirgenes KV, Thomassen K, Carlotti K, Erwin A, Lazier J, Marquardt T, He M, Edmondson AC, Izumi K. Genet Med. 2022 Jun;24(6):1227-1237. doi: 10.1016/j.gim.2022.02.005. Epub 2022 Mar 14.

Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement. Mahajan S, Ng BG, AlAbdi L, Earnest PDJ, Sosicka P, Patel N, Helaby R, Abdulwahab F, He M, Alkuraya FS, Freeze HH. J Med Genet. 2022 Nov 10:jmg-2022-108821. doi: 10.1136/jmg-2022-108821. Epub ahead of print. PMID: 36357165.

Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Defects in Golgi enzymes, which play a critical role in N-glycan processing and brain development, are often defined as types of CDG. However, defects in the Golgi enzyme MAN2A2 have not been known to cause defects in glycosylation. In this study, researchers investigated the effects of variants in MAN2A2. In a family of affected individuals, the team performed exome sequencing, analyzed N-glycans, and designed a cell-based complementation assay to evaluate the disease-causing effects of the variant. Findings show that variants in MAN2A2 cause a new type of CDG, which is characterized by neurological involvement and facial dysmorphism. Authors note that the cell-based complementation assay designed in this study can also help diagnose patients with potentially pathogenic variants in a very similar enzyme, MAN2A1.

N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts. Budhraja R, Saraswat M, De Graef D, Ranatunga W, Ramarajan MG, Mousa J, Kozicz T, Pandey A, Morava E. J Inherit Metab Dis. 2022 Sep 14. doi: 10.1002/jimd.12557. Epub ahead of print. PMID: 36102038.

NGLY1-CDDG (congenital disorder of deglycosylation) is a multisystemic, inherited condition caused by a mutation in the NGLY1 gene. Although the NGLY1 enzyme plays an essential role in the process of deglycosylation, the effects of NGLY1 deficiency on protein glycosylation are not yet understood. In this study, researchers explored the hypothesis that NGLY1 deficiency leads to accumulation of misfolded glycoproteins. Using glycoproteomics and proteomics methods, the team analyzed fibroblasts from four patients with NGLY1 deficiency carrying different variants in NGLY1. Results showed no significant accumulation of glycoproteins in the NGLY1-deficient fibroblasts. However, researchers found distinct changes in specific glycoproteins. As the first study of its kind, authors note that these findings highlight new insights for understanding NGLY1-CDDG.

Nutrition interventions in congenital disorders of glycosylation. Boyer SW, Johnsen C, Morava E. Trends Mol Med. 2022 Jun;28(6):463-481. doi: 10.1016/j.molmed.2022.04.003. Epub 2022 May 10.

Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions. Sosicka P, Ng BG, Pepi LE, Shajahan A, Wong M, Scott DA, Matsumoto K, Xia ZJ, Lebrilla CB, Haltiwanger RS, Azadi P, Freeze HH. J Cell Biol. 2022 Oct 3;221(10):e202205038. doi: 10.1083/jcb.202205038. Epub 2022 Sep 2. PMID: 36053214.

Congenital disorders of glycosylation (CDG) are a group of inherited metabolic disorders that affect a process called glycosylation. This process uses monosaccharides (simple sugars) from multiple sources to produce nucleotide sugars (activated forms of monosaccharides). Since these sources of monosaccharides are assumed to contribute to one similar pool, their individual contributions are often overlooked. In this study, researchers explored the hypothesis that fucose (a type of monosaccharide) exists in multiple, distinct pools. The team measured the contribution of fucose from different sources. Findings show that cells identify and select from different pools of fucose for the process of glycosylation. Authors also present new perspectives on monosaccharide metabolism, which may have other applications beyond glycosylation.

Patient-reported outcomes and quality of life in PMM2-CDG. Ligezka AN, Mohamed A, Pascoal C, Ferreira VDR, Boyer S, Lam C, Edmondson A, Krzysciak W, Golebiowski R, Perez-Ortiz J, Morava E. Mol Genet Metab. 2022 Jun;136(2):145-151. doi: 10.1016/j.ymgme.2022.04.002. Epub 2022 Apr 20.

Successful heart transplantation in an infant with phosphoglucomutase 1 deficiency (PGM1-CDG). Altassan R, Albert-Brotons DC, Alowain M, Al-Halees Z, Jaeken J, Morava E. JIMD Rep. 2022 Nov 22;64(2):123-128. doi: 10.1002/jmd2.12350. eCollection 2023 Mar.

A new D-galactose treatment monitoring index for PGM1-CDG. Perales-Clemente E, Liedtke K, Studinski A, Radenkovic S, Gavrilov D, Oglesbee D, Matern D, Rinaldo P, Tortorelli S, Morava E, Raymond K. J Inherit Metab Dis. 2021 Sep;44(5):1263-1271. doi: 10.1002/jimd.12406. Epub 2021 Jun 22.

ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. Alsharhan H, He M, Edmondson AC, Daniel EJP, Chen J, Donald T, Bakhtiari S, Amor DJ, Jones EA, Vassallo G, Vincent M, Cogné B, Deb W, Werners AH, Jin SC, Bilguvar K, Christodoulou J, Webster RI, Yearwood KR, Ng BG, Freeze HH, Kruer MC, Li D, Raymond KM, Bhoj EJ, Sobering AK. J Inherit Metab Dis. 2021 Mar 18. doi: 10.1002/jimd.12378. Online ahead of print.

Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings. Wilson MP, Garanto A, Pinto E Vairo F, Ng BG, Ranatunga WK, Ventouratou M, Baerenfaenger M, Huijben K, Thiel C, Ashikov A, Keldermans L, Souche E, Vuillaumier-Barrot S, Dupré T, Michelakakis H, Fiumara A, Pitt J, White SM, Lim SC, Gallacher L, Peters H, Rymen D, Witters P, Ribes A, Morales-Romero B, Rodríguez-Palmero A, Ballhausen D, de Lonlay P, Barone R, Janssen MCH, Jaeken J, Freeze HH, Matthijs G, Morava E, Lefeber DJ. Am J Hum Genet. 2021 Nov 4;108(11):2130-2144. doi: 10.1016/j.ajhg.2021.09.012. Epub 2021 Oct 14. PMID: 34653363; PMCID: PMC8595932.

Congenital disorders of glycosylation (CDGs) are a group of rare diseases characterized by hypoglycosylation. The STT3A gene plays an essential role in protein N-glycosylation. In this study, researchers identified 16 individuals from nine families who have variants in STT3A, leading to an autosomal-dominant CDG. They describe the features of these individuals including variable skeletal anomalies, short stature, large head, muscle cramps, and in some, intellectual disability. The authors also present data to support a dominant form of STT3A-CDG that is unusual among type I CDGs.

Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation. Polla DL, Edmondson AC, Duvet S, March ME, Sousa AB, Lehman A; CAUSES Study, Niyazov D, van Dijk F, Demirdas S, van Slegtenhorst MA, Kievit AJA, Schulz C, Armstrong L, Bi X, Rader DJ, Izumi K, Zackai EH, de Franco E, Jorge P, Huffels SC, Hommersom M, Ellard S, Lefeber DJ, Santani A, Hand NJ, van Bokhoven H, He M, de Brouwer APM. Am J Hum Genet. 2021 Jul 1;108(7):1342-1349. doi: 10.1016/j.ajhg.2021.05.010. Epub 2021 Jun 17.

D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial. Witters P, Andersson H, Jaeken J, Tseng L, van Karnebeek CDM, Lefeber DJ, Cassiman D, Morava E. Orphanet J Rare Dis. 2021 Mar 20;16(1):138. doi: 10.1186/s13023-020-01609-z.

Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation. Radenkovic S, Fitzpatrick-Schmidt T, Byeon SK, Madugundu AK, Saraswat M, Lichty A, Wong SYW, McGee S, Kubiak K, Ligezka A, Ranatunga W, Zhang Y, Wood T, Friez MJ, Clarkson K, Pandey A, Jones JR, Morava E. Mol Genet Metab. 2021 Jan;132(1):27-37. doi: 10.1016/j.ymgme.2020.10.007. Epub 2020 Oct 17.

Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG. Alsharhan H, Ng BG, Daniel EJP, Friedman J, Pivnick EK, Al-Hashem A, Faqeih EA, Liu P, Engelhardt NM, Keller KN, Chen J, Mazzeo PA; University of Washington Center for Mendelian Genomics (UW-CMG), Rosenfeld JA, Bamshad MJ, Nickerson DA, Raymond KM, Freeze HH, He M, Edmondson AC, Lam C. J Inherit Metab Dis. 2021 Feb 13. doi: 10.1002/jimd.12367. Online ahead of print.

Genotype-Phenotype Correlations in PMM2-CDG. Vaes L, Rymen D, Cassiman D, Ligezka A, Vanhoutvin N, Quelhas D, Morava E, Witters P Genotype-Phenotype Correlations in PMM2-CDG . Genes (Basel). 2021 Oct 21;12(11):1658. doi: 10.3390/genes12111658. PMID: 34828263; PMCID: PMC8620515.

PMM2-CDG is a rare disease that causes hypoglycosylation of multiple proteins. Direct genotype-phenotype correlations are not yet identified. In this paper, researchers carried out a retrospective cohort study on 26 PMM2-CDG patients. They collected the identified genotype, as well as variables indicating the disease severity and patients' phenotype. By studying the phenotypic effects of patients' genotype, researchers gained a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base. They concluded that specific pathogenic variants (p.Pro113Leu and p.Phe119Leu) have a significantly higher total NPCRS disease severity score which indicates a more severe clinical outcome. The Nijmegen Paediatric CDG Rating Scale (NPCRS) is a tool to objectively follow the clinical disease progression in clinical disorders of glycosylation (CDG). Pathogenic variants affecting the folding or stabilization domain of the PMM2 enzyme protein have a significantly lower total NPCRS and thus the genetic results could provide a good prognostic clinical outcome.

Immune dysfunction in MGAT2-CDG: A clinical report and review of the literature. Poskanzer SA, Schultz MJ, Turgeon CT, Vidal-Folch N, Liedtke K, Oglesbee D, Gavrilov DK, Tortorelli S, Matern D, Rinaldo P, Bennett JT, Thies JM, Chang IJ, Beck AE, Raymond K, Allenspach EJ, Lam C. Am J Med Genet A. 2021 Jan;185(1):213-218. doi: 10.1002/ajmg.a.61914. Epub 2020 Oct 12.

Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder. Morava E, Schatz UA, Torring PM, Abbott MA, Baumann M, Brasch-Andersen C, Chevalier N, Dunkhase-Heinl U, Fleger M, Haack TB, Nelson S, Potelle S, Radenkovic S, Bommer GT, Van Schaftingen E, Veiga-da-Cunha M. Am J Hum Genet. 2021 Jun 3;108(6):1151-1160. doi: 10.1016/j.ajhg.2021.04.017. Epub 2021 May 11.

Study authors describe a genetic syndrome due to PGM2L1 deficiency. The gene PGM2L1 is highly expressed in the brain. They report the identification of four children with PGM2L1 deficiency sharing a largely neurological phenotype. All four children had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Study authors concluded that, while analyses indicated PGM2L1 deficiency does not appear to be a glycosylation defect, the discovery of this developmental disorder highlights the importance of glucose-1,6-biophosphate in the brain.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management. Altassan R, Radenkovic S, Edmondson AC, Barone R, Brasil S, Cechova A, Coman D, Donoghue S, Falkenstein K, Ferreira V, Ferreira C, Fiumara A, Francisco R, Freeze H, Grunewald S, Honzik T, Jaeken J, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-da-Silva D, Pascoal C, Quelhas D, Raymond KM, Rymen D, Seroczynska M, Serrano M, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Voermans N, Witters P, Morava E. J Inherit Metab Dis. 2021 Jan;44(1):148-163. doi: 10.1002/jimd.12286. Epub 2020 Sep 15.

Is X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy a congenital disorder of glycosylation?. Berry GT, Freeze HH, Morava E. Epilepsia. 2021 Feb;62(2):335-336. doi: 10.1111/epi.16817. Epub 2021 Feb 11.

Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up. Starosta RT, Boyer S, Tahata S, Raymond K, Lee HE, Wolfe LA, Lam C, Edmondson AC, Schwartz IVD, Morava E. Orphanet J Rare Dis. 2021 Jan 7;16(1):20. doi: 10.1186/s13023-020-01630-2.

Manifestations and Management of Hepatic Dysfunction in Congenital Disorders of Glycosylation. Johnsen C, Edmondson AC.. Clin Liver Dis (Hoboken). 2021 Sep 19;18(2):54-66. doi: 10.1002/cld.1105. eCollection 2021 Aug.

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?. Čechová A, Honzík T, Edmondson AC, Ficicioglu C, Serrano M, Barone R, De Lonlay P, Schiff M, Witters P, Lam C, Patterson M, Janssen MCH, Correia J, Quelhas D, Sykut-Cegielska J, Plotkin H, Morava E, Sarafoglou K. Mol Genet Metab. 2021 Aug;133(4):397-399. doi: 10.1016/j.ymgme.2021.06.003. Epub 2021 Jun 11.

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications. Ligezka AN, Radenkovic S, Saraswat M, Garapati K, Ranatunga W, Krzysciak W, Yanaihara H, Preston G, Brucker W, McGovern RM, Reid JM, Cassiman D, Muthusamy K, Johnsen C, Mercimek-Andrews S, Larson A, Lam C, Edmondson AC, Ghesquière B, Witters P, Raymond K, Oglesbee D, Pandey A, Perlstein EO, Kozicz T, Morava E. Ann Neurol. 2021 Dec;90(6):887-900. doi: 10.1002/ana.26245. Epub 2021 Oct 26.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study. Witters P, Edmondson AC, Lam C, Johnsen C, Patterson MC, Raymond KM, He M, Freeze HH, Morava E. Orphanet J Rare Dis. 2021 Feb 25;16(1):102. doi: 10.1186/s13023-021-01751-2.

Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy. Del Caño-Ochoa F, Ng BG, Abedalthagafi M, Almannai M, Cohn RD, Costain G, Elpeleg O, Houlden H, Karimiani EG, Liu P, Manzini MC, Maroofian R, Muriello M, Al-Otaibi A, Patel H, Shimon E, Sutton VR, Toosi MB, Wolfe LA, Rosenfeld JA, Freeze HH, Ramón-Maiques S. Genet Med. 2020 Oct;22(10):1598-1605. doi: 10.1038/s41436-020-0833-2. Epub 2020 May 28.

Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG. Witters P, Tahata S, Barone R, Õunap K, Salvarinova R, Grønborg S, Hoganson G, Scaglia F, Lewis AM, Mori M, Sykut-Cegielska J, Edmondson A, He M, Morava E. Genet Med. 2020 Jun;22(6):1102-1107. doi: 10.1038/s41436-020-0767-8. Epub 2020 Feb 27.

Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation. Čechová A, Altassan R, Borgel D, Bruneel A, Correia J, Girard M, Harroche A, Kiec-Wilk B, Mohnike K, Pascreau T, Pawliński Ł, Radenkovic S, Vuillaumier-Barrot S, Aldamiz-Echevarria L, Couce ML, Martins EG, Quelhas D, Morava E, de Lonlay P, Witters P, Honzík T. J Inherit Metab Dis. 2020 Jul;43(4):671-693. doi: 10.1002/jimd.12241. Epub 2020 Apr 21.

Defining a new immune deficiency syndrome: MAN2B2-CDG. Verheijen J, Wong SY, Rowe JH, Raymond K, Stoddard J, Delmonte OM, Bosticardo M, Dobbs K, Niemela J, Calzoni E, Pai SY, Choi U, Yamazaki Y, Comeau AM, Janssen E, Henderson L, Hazen M, Berry G, Rosenzweig SD, Aldhekri HH, He M, Notarangelo LD, Morava E. J Allergy Clin Immunol. 2020 Mar;145(3):1008-1011. doi: 10.1016/j.jaci.2019.11.016. Epub 2019 Nov 24.

Fetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype. Ferrer A, Starosta RT, Ranatunga W, Ungar D, Kozicz T, Klee E, Rust LM, Wick M, Morava E. Mol Genet Metab. 2020 Dec;131(4):424-429. doi: 10.1016/j.ymgme.2020.11.003. Epub 2020 Nov 7.

Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Zilmer M, Edmondson AC, Khetarpal SA, Alesi V, Zaki MS, Rostasy K, Madsen CG, Lepri FR, Sinibaldi L, Cusmai R, Novelli A, Issa MY, Fenger CD, Abou Jamra R, Reutter H, Briuglia S, Agolini E, Hansen L, Petäjä-Repo UE, Hintze J, Raymond KM, Liedtke K, Stanley V, Musaev D, Gleeson JG, Vitali C, O'Brien WT, Gardella E, Rubboli G, Rader DJ, Schjoldager KT, Møller RS. Brain. 2020 Apr 1;143(4):1114-1126. doi: 10.1093/brain/awaa063.

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions. Ng BG, Eklund EA, Shiryaev SA, Dong YY, Abbott MA, Asteggiano C, Bamshad MJ, Barr E, Bernstein JA, Chelakkadan S, Christodoulou J, Chung WK, Ciliberto MA, Cousin J, Gardiner F, Ghosh S, Graf WD, Grunewald S, Hammond K, Hauser NS, Hoganson GE, Houck KM, Kohler JN, Morava E, Larson AA, Liu P, Madathil S, McCormack C, Meeks NJL, Miller R, Monaghan KG, Nickerson DA, Palculict TB, Papazoglu GM, Pletcher BA, Scheffer IE, Schenone AB, Schnur RE, Si Y, Rowe LJ, Serrano Russi AH, Russo RS, Thabet F, Tuite A, Villanueva MM, Wang RY, Webster RI, Wilson D, Zalan A; Undiagnosed Diseases Network, University of Washington Center for Mendelian Genomics (UW-CMG), Wolfe LA, Rosenfeld JA, Rhodes L, Freeze HH. J Inherit Metab Dis. 2020 Nov;43(6):1333-1348. doi: 10.1002/jimd.12290. Epub 2020 Aug 5.

Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature. Qian Z, Van den Eynde J, Heymans S, Mertens L, Morava E. JIMD Rep. 2020 Aug 19;56(1):27-33. doi: 10.1002/jmd2.12160. eCollection 2020 Nov.

Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG. Iyer S, Sam FS, DiPrimio N, Preston G, Verheijen J, Murthy K, Parton Z, Tsang H, Lao J, Morava E, Perlstein EO. Dis Model Mech. 2019 Nov 11;12(11):dmm040584. doi: 10.1242/dmm.040584.

Airway Disease in Children with Primary Ciliary Dyskinesia: Impact of Ciliary Ultrastructure Defect and Genotype. Kinghorn B, Rosenfeld M, Sullivan E, Onchiri F, Ferkol TW, Sagel SD, Dell SD, Milla C, Shapiro AJ, Sullivan KM, Zariwala MA, Pittman JE, Mollica F, Tiddens HAWM, Kemner-van de Corput M, Knowles MR, Davis SD, Leigh MW. Ann Am Thorac Soc. 2023 Apr;20(4):539-547. doi: 10.1513/AnnalsATS.202206-524OC.

Airway Inflammation in Children with Primary Ciliary Dyskinesia. Sagel SD, Kupfer O, Wagner BD, Davis SD, Dell SD, Ferkol TW, Hoppe JE, Rosenfeld M, Sullivan KM, Tiddens HAWM, Knowles MR, Leigh MW. Ann Am Thorac Soc. 2023 Jan;20(1):67-74. doi: 10.1513/AnnalsATS.202204-314OC. PMID: 35984413; PMCID: PMC9819265.

Primary ciliary dyskinesia (PCD) is an inherited condition in which mucociliary clearance of the lungs is impaired. In this disorder, cilia (hairlike structures) lining the airway, sinuses, and middle ears have defective movements, leading to accumulation of harmful particles and pathogens trapped within mucus. Currently, not much is known about the role of airway inflammation in the development of PCD in children. In this study, researchers investigated the relationships between sputum (mucus) inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. The team collected spontaneously expectorated sputum from clinically stable children and adolescents with PCD ages six years and older. Next, the team correlated sputum protease and inflammatory cytokine concentrations with age, lung function, and chest computed tomography measures of structural lung disease. Results show that in this multicenter cohort of pediatric patients with PCD, elevated concentrations of sputum proteases and cytokines were associated with impaired lung function and structural damage as determined by chest computed tomography. These results establish an important linkage between airway inflammation and lung disease in PCD. Authors note that these findings also suggest sputum inflammatory measurements could serve as biomarkers in PCD and could be used to assess the efficacy of anti-inflammatory therapies.

First reports of primary ciliary dyskinesia caused by a shared DNAH11 allele in Canadian Inuit. Hunter-Schouela J, Geraghty MT, Hegele RA, Dyment DA, St Pierre D, Richer J, Sheffield H, Zariwala MA, Knowles MR, Lehman A, Dell S, Shapiro AJ, Kovesi TA. Pediatr Pulmonol. 2023 Jul;58(7):1942-1949. doi: 10.1002/ppul.26414. Epub 2023 Apr 23.

HYDIN Variants Are a Common Cause of Primary Ciliary Dyskinesia in French Canadians. Shapiro AJ, Sillon G, D'Agostino D, Baret L, López-Giráldez F, Mane S, Leigh MW, Davis SD, Knowles MR, Zariwala MA. Ann Am Thorac Soc. 2023 Jan;20(1):140-144. doi: 10.1513/AnnalsATS.202203-253RL. PMID: 36112114; PMCID: PMC9819264.

Primary ciliary dyskinesia (PCD) is a genetic disorder in which mucociliary clearance of the lungs is impaired. In the past two decades, more than 50 PCD-related genes have been discovered. However, most commercial genetic panels do not include variant analysis of the large, complex PCD gene HYDIN. In this letter to the editor, researchers discuss a study of 28 patients in 21 families with probable but undiagnosed PCD from the PCD clinic at McGill University Health Centre in Montreal, Quebec, Canada. To investigate whether HYDIN played a role in these unsolved cases, the team utilized whole-exome sequencing and next-generation sequencing analyses. Results show that pathogenic variants in HYDIN aided diagnosis in six of 21 families with previously unsolved PCD. These findings show that HYDIN variants are responsible for a large percentage of PCD in Quebec. Although it is not clear if increased HYDIN prevalence will be observed in populations outside of Quebec, authors state that transitioning to commercial panels that analyze HYDIN seems critical to accurately diagnose patients with PCD.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis. Kim S, Li L, Lin FC, Stack T, Lamb MM, Mohammad I, Norris M, Klatt-Cromwell C, Thorp BD, Ebert CS Jr, Masters D, Senior BA, Askin FB, Kimple AJ. Int Forum Allergy Rhinol. 2023 Nov 23. doi: 10.1002/alr.23303. Epub ahead of print. PMID: 37997295

Primary ciliary dyskinesia (PCD) is an inherited condition in which mucociliary clearance of the lungs is impaired, leading to accumulation of harmful particles and pathogens trapped within mucus. In addition to lung disease, this results in chronic rhinosinusitis, where the lining of the sinuses becomes swollen, creates extra mucus, and interferes with drainage.

In this study, researchers characterized the histologic change (microscopic changes in tissues) of PCD-related chronic rhinosinusitis (PCD-CRS) in individuals with PCD who underwent sinus surgery. The team compared tissue samples from patients with PCD-CRS to those with cystic fibrosis-related chronic rhinosinusitis (CF-CRS), routine chronic rhinosinusitis without nasal polyps, and healthy controls.  

While sinus disease is generally mediated by eosinophils (a specific white blood cell) in PCD-CRS, neutrophils were the dominant immune cell in sinus tissue, similar to CF-CRS. As targeted therapies become available for CRS, understanding the pathogenesis of PCD-CRS becomes increasingly important.  

Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype. Barber AT, Shapiro AJ, Davis SD, Ferkol TW, Atkinson JJ, Sagel SD, Dell SD, Olivier KN, Milla CE, Rosenfeld M, Li L, Lin FC, Sullivan KM, Capps NA, Zariwala MA, Knowles MR, Leigh MW. Ann Am Thorac Soc. 2023 Mar;20(3):397-405. doi: 10.1513/AnnalsATS.202206-487OC. PMID: 36342963; PMCID: PMC9993158.

Primary ciliary dyskinesia (PCD) is an inherited disorder which affects the movement of tiny hair-like structures on body cells known as cilia, impairing mucociliary clearance of the lungs. Approximately 50 percent of PCD patients have a laterality defect (right-left placement of organs in the chest and abdomen) attributable to impaired ciliary motility in the early embryo. The association between abnormalities in organ laterality and the PCD-associated defect of ciliary ultrastructure (fine, detailed structure) or genotype is not well understood.

In this study, researchers investigated the association between presence and/or type of laterality abnormality and ciliary ultrastructural defect or genotype in PCD. First, the team grouped 559 participants with PCD based on ciliary ultrastructural defect or genotype. Next, researchers analyzed the data to evaluate the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality.

Results show that in patients with PCD, risk of a laterality abnormality differs by ciliary ultrastructural defect. Authors note that further research is needed to understand the pathophysiologic mechanisms underlying these differences.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard. Beydon N, Kouis P, Marthin JK, Latzin P, Colas M, Davis SD, Haarman E, Harris AL, Hogg C, Kilbride E, Kuehni CE, Marangu D, Nielsen KG, Pendergrast C, Robinson P, Rumman N, Rutter M, Walker WT, Ferkol T, Lucas JS. Eur Respir J. 2023 Apr 20;61(4):2202031. doi: 10.1183/13993003.02031-2022. Print 2023 Apr.

Primary ciliary dyskinesia: An update on contemporary diagnosis. Chaskes MB, Lopez EM, Kong KA, Ebert CS Jr, Senior BA, Thorp BD, Kimple AJ. Int Forum Allergy Rhinol. 2023 Aug 11. doi: 10.1002/alr.23254. Epub ahead of print. PMID: 37565263

Primary ciliary dyskinesia (PCD) is an inherited condition in which mucociliary clearance of the lungs is impaired. Symptoms include chronic sinusitis, frequent respiratory and middle ear infections, hearing loss, chronic cough, severe lung damage, and bronchiectasis (irreversible scarring and dilation of the bronchi).

Individuals with PCD often receive a delayed diagnosis due to multiple factors, including the commonality of symptoms, variability of severity, number of clinicians involved in their care, limitations of diagnostic tests, and lack of standards. Both diagnosed and undiagnosed individuals with PCD require frequent care of the ear, nose, and throat (ENT). However, there is limited published guidance for the proper diagnosis of PCD.  

This clinical letter for ENT clinicians educates ENTs about modern diagnostic criteria and considerations through two cases: a new diagnosis in an adult and a misdiagnosis of PCD as a child that was carried into adulthood. 

Response to letter to the editor regarding "Sinonasal quality of life in primary ciliary dyskinesia". Stack TJ, Norris M, Mohammad I, Thorp BD, Klatt-Cromwell C, Ebert CS Jr, Senior BA, Kimple AJ. Int Forum Allergy Rhinol. 2023 Nov 8. doi: 10.1002/alr.23297. Online ahead of print.

Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team. Lancet Respir Med. 2023 Aug 31:S2213-2600(23)00226-6. doi: 10.1016/S2213-2600(23)00226-6. Online ahead of print.

Sinonasal quality of life in primary ciliary dyskinesia. Stack T, Norris M, Kim S, Lamb M, Zeatoun A, Mohammad I, Worden C, Thorp BD, Klatt-Cromwell C, Ebert CS Jr, Senior BA, Kimple AJ. Int Forum Allergy Rhinol. 2023 May 19. doi: 10.1002/alr.23180. Online ahead of print.

A Deep Intronic, Pathogenic Variant in DNAH11 Causes Primary Ciliary Dyskinesia. Shapiro AJ, Stonebraker JR, Knowles MR, Zariwala MA. Am J Respir Cell Mol Biol. 2022 Oct;67(4):511-514. doi: 10.1165/rcmb.2022-0176LE.

Association of Neonatal Hospital Length of Stay with Lung Function in Primary Ciliary Dyskinesia. Wee WB, Leigh MW, Davis SD, Rosenfeld M, Sullivan KM, Sawras MG, Ferkol TW, Knowles MR, Milla C, Sagel SD, Zariwala MA, Pullenayegum E, Dell SD. Ann Am Thorac Soc. 2022 Nov;19(11):1865-1870. doi: 10.1513/AnnalsATS.202202-116OC. PMID: 35657736.

Primary ciliary dyskinesia (PCD) is an inherited, multisystem disease affecting the airways, sinuses, and middle ear that arises from dysfunctional cilia (hairlike structures). This in turn can lead to hearing loss, chronic cough, severe lung damage, and bronchiectasis (irreversible scarring and dilation of the bronchi). Patients with PCD have ranging disease variability and severity, with some clinical manifestations presenting soon after birth. In this study, researchers evaluated the association between neonatal hospital length of stay and supplemental oxygen duration with lung function in pediatric PCD. They used data from a Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) multicenter study consisting of 123 pediatric patients with PCD followed over 5 years. Study results showed that neonatal hospital length of stay was associated with worse lung function, independent of age and ultrastructural defects. However, supplemental oxygen duration was not associated with lung function. These findings highlight the need for future research into the mechanisms and management of neonatal respiratory distress in PCD patients to better understand the variability in lung health outcomes in this patient population.

Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype. Ostrowski LE, Yin W, Smith AJ, Sears PR, Bustamante-Marin XM, Dang H, Hildebrandt F, Daniels LA, Capps NA, Sullivan KM, Leigh MW, Zariwala MA, Knowles MR Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype. Int J Mol Sci. 2022 Feb 3;23(3):1753. doi: 10.3390/ijms23031753. PMID: 35163670; PMCID: PMC8835943.

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the movement of cilia, tiny hair-like structures on airway cells that beat rhythmically to move mucus out of the airways. Defects in cilia structure or function result in chronic upper and lower respiratory disease. Mutations in the ODAD1 gene result in a failure to assemble outer dynein arms (ODAs), the molecular motors that provide the force for ciliary beating. In the absence of ODAD1, cilia are mostly immotile cilia, and subjects suffer from a typical PCD phenotype. In this study, researchers identified a patient with an unusually mild phenotype and a mutation in ODAD1. To investigate the mechanisms behind this unusual phenotype, they performed molecular and functional studies of cultured nasal epithelial cells. Their findings indicate that the mutant protein retains partial function, allowing for the assembly of some ODAs and a significant level of ciliary activity that may result in the unusually mild phenotype. These findings also suggest that partial restoration of ciliary function by therapeutic agents could lead to significant improvement of PCD symptoms.

Going beyond the chest X-ray: Investigating laterality defects in primary ciliary dyskinesia. Wee WB, Kaspy KR, Sawras MG, Knowles MR, Zariwala MA, Leigh MW, Dell SD, Shapiro AJ. Pediatr Pulmonol. 2022 May;57(5):1318-1324. doi: 10.1002/ppul.25853. Epub 2022 Feb 21. PMID: 35122416.

Primary ciliary dyskinesia (PCD) is an inherited condition in which mucociliary clearance is impaired in the upper and lower airways. Organ laterality defects are common in patients with PCD, ranging from situs inversus totalis (SIT, complete mirror image organ arrangement), to situs ambiguus (SA, any laterality defect other than SI). However, targeted investigations for these defects are not universally recommended in PCD consensus statements. Without investigations beyond chest radiography (CXR), clinically significant defects may go undetected, leading to increased morbidity. In this study, researchers reviewed CXR images and reports of add-on, targeted investigations (computed tomography scans, abdominal ultrasounds, upper GI contrast studies, and splenic scintigraphy) from medical records collected at two PCD clinics. They compared situs classifications from CXR alone versus CXR with add-on, targeted investigations. Results showed that situs classification differed significantly from CXR images alone versus CXR with add-on, targeted investigations. Some of these additional organ laterality defects resulted in significant patient morbidity and even mortality when splenic dysfunction was present. Authors conclude that in PCD patients, clinically significant SA defects may not be detected by CXR alone. These results suggest that the routine use of CXR with add-on, targeted investigations may be justified.

Hereditary Mucin Deficiency Caused by Biallelic Loss of Function of MUC5B. Costain G, Liu Z, Mennella V, Radicioni G, Goczi AN, Albulescu A, Walker S, Ngan B, Manson D, Vali R, Khan M, Palaniyar N, Hill DB, Hall DA, Marshall CR, Knowles M, Zariwala MA, Kesimer M, Dell SD. Am J Respir Crit Care Med. 2022 Apr 1;205(7):761-768. doi: 10.1164/rccm.202106-1456OC. PMID: 35023825.

Mucins (the major protein component of mucus) are fundamental to airway health. Upregulation of mucin 5B (MUC5B) is observed in common lung diseases, making it a potential therapeutic target. In mice, Muc5b is required for mucociliary clearance and for controlling inflammation after microbial exposure, although the consequences of its loss in humans are unclear. In this study, researchers aimed to identify and characterize a family with congenital absence of MUC5B. The team performed whole-genome sequencing in an adult proband, deep phenotyping, and genotyping with reverse phenotyping for 8 family members. Across accessible sample types, the team performed immunofluorescence staining and mass spectrometry for mucins. Results show that congenital absence of MUC5B defines a new category of genetic respiratory disease. In addition, the human phenotype is consistent with the Muc5b mouse model. Authors note that further study of individuals with decreased MUC5B production could provide unique insights into airway mucus biology.

Otolaryngology Manifestations of Primary Ciliary Dyskinesia: A Multicenter Study. Zawawi F, Shapiro AJ, Dell S, Wolter NE, Marchica CL, Knowles MR, Zariwala MA, Leigh MW, Smith M, Gajardo P, Daniel SJ. Otolaryngol Head Neck Surg. 2022 Mar;166(3):540-547. doi: 10.1177/01945998211019320. Epub 2021 Jun 22.

The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia. Smith AJ, Bustamante-Marin XM, Yin W, Sears PR, Herring LE, Dicheva NN, López-Giráldez F, Mane S, Tarran R, Leigh MW, Knowles MR, Zariwala MA, Ostrowski LE. J Cell Sci. 2022 Mar 15;135(6):jcs259512. doi: 10.1242/jcs.259512. Epub 2022 Mar 31.

Autosomal dominant variants in FOXJ1 causing primary ciliary dyskinesia in two patients with obstructive hydrocephalus. Shapiro AJ, Kaspy K, Daniels MLA, Stonebraker JR, Nguyen VH, Joyal L, Knowles MR, Zariwala MA. Mol Genet Genomic Med. 2021 Jul;9(7):e1726. doi: 10.1002/mgg3.1726. Epub 2021 Jun 15.

Two patients with chronic oto-sino-pulmonary disease and hydrocephalus underwent candidate testing of FOXJ1, a gene that controls the production of motile cilia (miniature, whip-like organelles in the lungs, respiratory tract and middle ear, whose beating generates a directional fluid flow). Upon sequencing, heterozygous, pathogenic variants were discovered in two patients. Study authors concluded that FOXJ1 pathogenic variants cause primary ciliary dyskinesia (PCD) in a de novo, autosomal dominant inheritance pattern, and are associated with hydrocephalus. Physicians treating patients with hydrocephalus and chronic oto-sino-pulmonary disease should be aware of this PCD association and test for FOXJ1 variants.

Early Diagnosis and Intervention in Cystic Fibrosis: Imagining the Unimaginable. Coverstone AM, Ferkol TW. Front Pediatr. 2021 Jan 11;8:608821. doi: 10.3389/fped.2020.608821. eCollection 2020.

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia. Brennan SK, Ferkol TW, Davis SD. Int J Mol Sci. 2021 Jul 31;22(15):8272. doi: 10.3390/ijms22158272.

Primary ciliary dyskinesia (PCD) is a rare inherited condition that affects cilia—tiny, hair-like structures—in the lungs, nose and ears of affected individuals, both impairing their ability to remove germs and pollutants and allowing mucus buildup and infections. Abnormal cilia can alter fluid flow in the fallopian tubes and ventricles within the brain, and defects in analogous structures, flagella, can result in abnormal sperm movement. Approximately 50% of people with PCD will present with a laterality defect, like situs inversus totalis, in which the arrangement of the internal organs is a mirror image of normal anatomy. Heterotaxy, in which many organs in the body can be formed abnormally, in the wrong position, or even missing, is also more common in this disease. In this review paper, authors provide an overview of PCD and describe its impacts on cilia structure and function as well as diagnostic approaches. They summarize the various types and presentations (phenotypes) of PCD along with causative genes (genotypes) and the relationships that have emerged over 20 years of research into the condition. Authors also state that the increasing availability of genetic panels for PCD are now refining their understanding of those genotype-phenotype relationships and revealing milder forms of the disease.

Implementation of a screening tool for primary ciliary dyskinesia (PCD) in a pediatric otolaryngology clinic. Brennan SK, Molter D, Menezes M, Dunsky K, Leonard D, Lieu J, Hirose K, Hazan G, Horani A, Ferkol T, Brody SL. Int J Pediatr Otorhinolaryngol. 2021 Mar;142:110586. doi: 10.1016/j.ijporl.2020.110586. Epub 2020 Dec 31.

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort. Pappa AK, Sullivan KM, Lopez EM, Adams KN, Zanation AM, Ebert CS Jr, Thorp BD, Senior BA, Leigh MW, Knowles MR, Kimple AJ. Am J Rhinol Allergy. 2021 Jan;35(1):72-76. doi: 10.1177/1945892420933175. Epub 2020 Jun 19.

Structural insights into the cause of human RSPH4A primary ciliary dyskinesia. Zhao Y, Pinskey J, Lin J, Yin W, Sears PR, Daniels LA, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. Mol Biol Cell. 2021 Jun 1;32(12):1202-1209. doi: 10.1091/mbc.E20-12-0806. Epub 2021 Apr 14.

Understanding Primary Ciliary Dyskinesia and Other Ciliopathies. Horani A, Ferkol TW. J Pediatr. 2021 Mar;230:15-22.e1. doi: 10.1016/j.jpeds.2020.11.040. Epub 2020 Nov 23.

Use caution interpreting nasal nitric oxide – overlap in primary ciliary dyskinesia and primary immunodeficiency. Barber AT, Davis SD, Boutros H, Zariwala M, Knowles MR, Leigh MW. Pediatr Pulmonol. 2021 Sep 2. doi: 10.1002/ppul.25636. Online ahead of print.

This case report highlights the difficulty distinguishing primary ciliary dyskinesia (PCD) from primary immunodeficiency (PID) with particular emphasis on the potential overlap in nasal nitric oxide levels between the two disorders. An 11-year-old female with history of chronic wet cough, chronic nasal congestion, and recurrent lower respiratory tract infections was referred for evaluation of possible PCD. Her nasal nitric oxide level was low (9.8 nL/min) and remained low at follow-up one year later (17.5 nL/min). Ciliary ultrastructure on transmission electron microscopy (TEM) was normal and PCD genetic testing was unrevealing, but given her clinical history and low nasal nitric oxide, she was classified as “probable PCD.” Later, at the age of 21, she became acutely ill, was diagnosed with hemophagocytic lymphohistiocytosis, and died secondary to this. She was subsequently found to have a pathogenic variant in GATA2 resulting in GATA2 deficiency, a syndrome characterized by immunodeficiency and predisposition to myelodysplastic syndrome. This case illustrates how individuals with PID can also have persistent low nasal nitric oxide levels. In those with suspicion for PCD but without a definitive diagnosis (confirmed by either PCD genetic testing and/or abnormal ciliary ultrastructure on TEM), clinicians should consider genetic testing for PID.

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Chivukula RR, Montoro DT, Leung HM, Yang J, Shamseldin HE, Taylor MS, Dougherty GW, Zariwala MA, Carson J, Daniels MLA, Sears PR, Black KE, Hariri LP, Almogarri I, Frenkel EM, Vinarsky V, Omran H, Knowles MR, Tearney GJ, Alkuraya FS, Sabatini DM. Nat Med. 2020 Feb;26(2):244-251. doi: 10.1038/s41591-019-0730-x. Epub 2020 Jan 20.

A proposal for the addressing the needs of the pediatric pulmonary work force. Gaston B, Laguna TA, Noah TL, Hagood J, Voynow J, Ferkol T, Hershenson M, Boyne K, Delecaris A, Ross K, Gozal D, Celedón JC, Abman SH, Moore P, Davis S, Cornfield DN, Murphy T. Pediatr Pulmonol. 2020 Aug;55(8):1859-1867. doi: 10.1002/ppul.24856. Epub 2020 Jun 12.

Access to medicines for rare diseases: beating the drum for primary ciliary dyskinesia. Crowley S, Azevedo I, Boon M, Bush A, Eber E, Haarman E, Karadag B, Kötz K, Leigh M, Moreno-Galdó A, Mussaffi H, Nielsen KG, Omran H, Papon JF, Pohunek P, Priftis K, Rindlisbacher B, Santamaria F, Valiulis A, Witt M, Yiallouros P, Zivkovic Z, Kuehni CE, Lucas JS. ERJ Open Res. 2020 Sep 14;6(3):00377-2020. doi: 10.1183/23120541.00377-2020. eCollection 2020 Jul.

Author Correction: A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Chivukula RR, Montoro DT, Leung HM, Yang J, Shamseldin HE, Taylor MS, Dougherty GW, Zariwala MA, Carson J, Daniels MLA, Sears PR, Black KE, Hariri LP, Almogarri I, Frenkel EM, Vinarsky V, Omran H, Knowles MR, Tearney GJ, Alkuraya FS, Sabatini DM. Nat Med. 2020 Feb;26(2):300. doi: 10.1038/s41591-020-0773-z.

Comparison of Multiple Breath Washout and Spirometry in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis and Healthy Controls. Kinghorn B, McNamara S, Genatossio A, Sullivan E, Siegel M, Bauer I, Clem C, Johnson RC, Davis M, Griffiths A, Wheeler W, Johnson K, Davis SD, Leigh MW, Rosenfeld M, Pittman J. Ann Am Thorac Soc. 2020 Sep;17(9):1085-1093. doi: 10.1513/AnnalsATS.201905-375OC.

Cytoplasmic "ciliary inclusions" in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia. Vece TJ, Sagel SD, Zariwala MA, Sullivan KM, Burns KA, Dutcher SK, Yusupov R, Leigh MW, Knowles MR. Pediatr Pulmonol. 2020 Jan;55(1):130-135. doi: 10.1002/ppul.24528. Epub 2019 Sep 23.

HY-DIN' in the Cilia: Discovery of Central Pair-related Mutations in Primary Ciliary Dyskinesia. Dutcher SK, Brody SL. Am J Respir Cell Mol Biol. 2020 Mar;62(3):281-282. doi: 10.1165/rcmb.2019-0316ED.

High-Speed Videomicroscopy Analysis Presents Limitations in Diagnosis of Primary Ciliary Dyskinesia. Shapiro AJ, Ferkol TW, Manion M, Leigh MW, Davis SD, Knowles MR. Am J Respir Crit Care Med. 2020 Jan 1;201(1):122-123. doi: 10.1164/rccm.201907-1366LE.

Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia. Bustamante-Marin XM, Shapiro A, Sears PR, Charng WL, Conrad DF, Leigh MW, Knowles MR, Ostrowski LE, Zariwala MA. J Hum Genet. 2020 Jan;65(2):175-180. doi: 10.1038/s10038-019-0686-1. Epub 2019 Oct 21.

Limitations of Nasal Nitric Oxide Testing in Primary Ciliary Dyskinesia. Shapiro AJ, Davis SD, Leigh MW, Knowles MR, Lavergne V, Ferkol T. Am J Respir Crit Care Med. 2020 Aug 1;202(3):476-477. doi: 10.1164/rccm.202003-0835LE.

Motile ciliopathies. Wallmeier J, Nielsen KG, Kuehni CE, Lucas JS, Leigh MW, Zariwala MA, Omran H. Nat Rev Dis Primers. 2020 Sep 17;6(1):77. doi: 10.1038/s41572-020-0209-6.

Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia. Bustamante-Marin XM, Horani A, Stoyanova M, Charng WL, Bottier M, Sears PR, Yin WN, Daniels LA, Bowen H, Conrad DF, Knowles MR, Ostrowski LE, Zariwala MA, Dutcher SK. PLoS Genet. 2020 Aug 7;16(8):e1008691. doi: 10.1371/journal.pgen.1008691. eCollection 2020 Aug.

Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols. Shapiro AJ, Dell SD, Gaston B, O'Connor M, Marozkina N, Manion M, Hazucha MJ, Leigh MW. Ann Am Thorac Soc. 2020 Feb;17(2):e1-e12. doi: 10.1513/AnnalsATS.201904-347OT.

Primary ciliary dyskinesia in the genomics age. Lucas JS, Davis SD, Omran H, Shoemark A. Lancet Respir Med. 2020 Feb;8(2):202-216. doi: 10.1016/S2213-2600(19)30374-1. Epub 2019 Oct 14.

The Extrapulmonary Effects of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis. Sergeev V, Chou FY, Lam GY, Hamilton CM, Wilcox PG, Quon BS. Ann Am Thorac Soc. 2020 Feb;17(2):147-154. doi: 10.1513/AnnalsATS.201909-671CME.

The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial. Fowler C, Wu UI, Shaffer R, Smith C, Barnhart L, Bryant C, Olivier K, Holland SM. BMJ Open Respir Res. 2020 Mar;7(1):e000574. doi: 10.1136/bmjresp-2020-000574.

De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. Wallmeier J, Frank D, Shoemark A, Nöthe-Menchen T, Cindric S, Olbrich H, Loges NT, Aprea I, Dougherty GW, Pennekamp P, Kaiser T, Mitchison HM, Hogg C, Carr SB, Zariwala MA, Ferkol T, Leigh MW, Davis SD, Atkinson J, Dutcher SK, Knowles MR, Thiele H, Altmüller J, Krenz H, Wöste M, Brentrup A, Ahrens F, Vogelberg C, Morris-Rosendahl DJ, Omran H. Am J Hum Genet. 2019 Nov 7;105(5):1030-1039. doi: 10.1016/j.ajhg.2019.09.022. Epub 2019 Oct 17.

Errors in Methodology Affect Diagnostic Accuracy of High-Speed Videomicroscopy Analysis in Primary Ciliary Dyskinesia. Shapiro AJ, Leigh MW, Omran H, Lavergne V, Knowles MR. Chest. 2019 Nov;156(5):1032-1033. doi: 10.1016/j.chest.2019.06.021.

Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children. Vali R, Ghandourah H, Charron M, Nezhad KV, Omarkhail Y, Khazaee A, Shammas A, Dell SD. Pediatr Pulmonol. 2019 Dec;54(12):2021-2027. doi: 10.1002/ppul.24509. Epub 2019 Sep 12.

Frequenting Sequencing: How Genetics Teaches Us Cilia Biology. Horani A, Brody SL. Am J Respir Cell Mol Biol. 2019 Oct;61(4):403-404. doi: 10.1165/rcmb.2019-0103ED.

Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology. Takeda AJ, Maher TJ, Zhang Y, Lanahan SM, Bucklin ML, Compton SR, Tyler PM, Comrie WA, Matsuda M, Olivier KN, Pittaluga S, McElwee JJ, Long Priel DA, Kuhns DB, Williams RL, Mustillo PJ, Wymann MP, Koneti Rao V, Lucas CL. Nat Commun. 2019 Sep 25;10(1):4364. doi: 10.1038/s41467-019-12311-5.

Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance. Bustamante-Marin XM, Yin WN, Sears PR, Werner ME, Brotslaw EJ, Mitchell BJ, Jania CM, Zeman KL, Rogers TD, Herring LE, Refabért L, Thomas L, Amselem S, Escudier E, Legendre M, Grubb BR, Knowles MR, Zariwala MA, Ostrowski LE. Am J Hum Genet. 2019 Feb 7;104(2):229-245. doi: 10.1016/j.ajhg.2018.12.009. Epub 2019 Jan 18.

Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance. Ferré EMN, Break TJ, Burbelo PD, Allgäuer M, Kleiner DE, Jin D, Xu Z, Folio LR, Mollura DJ, Swamydas M, Gu W, Hunsberger S, Lee CR, Bondici A, Hoffman KW, Lim JK, Dobbs K, Niemela JE, Fleisher TA, Hsu AP, Snow LN, Darnell DN, Ojaimi S, Cooper MA, Bozzola M, Kleiner GI, Martinez JC, Deterding RR, Kuhns DB, Heller T, Winer KK, Rajan A, Holland SM, Notarangelo LD, Fennelly KP, Olivier KN, Lionakis MS. Sci Transl Med. 2019 Jun 5;11(495):eaav5597. doi: 10.1126/scitranslmed.aav5597.

Nasal Nitric Oxide in Primary Immunodeficiency and Primary Ciliary Dyskinesia: Helping to Distinguish Between Clinically Similar Diseases. Zysman-Colman ZN, Kaspy KR, Alizadehfar R, NyKamp KR, Zariwala MA, Knowles MR, Vinh DC, Shapiro AJ. J Clin Immunol. 2019 Feb;39(2):216-224. doi: 10.1007/s10875-019-00613-8. Epub 2019 Mar 26.

Patients with Idiopathic Pulmonary Nontuberculous Mycobacterial Disease Have Normal Th1/Th2 Cytokine Responses but Diminished Th17 Cytokine and Enhanced Granulocyte-Macrophage Colony-Stimulating Factor Production. Wu UI, Olivier KN, Kuhns DB, Fink DL, Sampaio EP, Zelazny AM, Shallom SJ, Marciano BE, Lionakis MS, Holland SM. Open Forum Infect Dis. 2019 Nov 28;6(12):ofz484. doi: 10.1093/ofid/ofz484. eCollection 2019 Dec.

Primary Ciliary Dyskinesia (PCD): A genetic disorder of motile cilia. Leigh MW, Horani A, Kinghorn B, O'Connor MG, Zariwala MA, Knowles MR. Transl Sci Rare Dis. 2019;4(1-2):51-75. doi: 10.3233/TRD-190036. Epub 2019 Jul 4.

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype. Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW. Am J Respir Crit Care Med. 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC.

Prospective multicenter randomized patient recruitment and sample collection to enable future measurements of sputum biomarkers of inflammation in an observational study of cystic fibrosis. Liou TG, Adler FR, Argel N, Asfour F, Brown PS, Chatfield BA, Daines CL, Durham D, Francis JA, Glover B, Heynekamp T, Hoidal JR, Jensen JL, Keogh R, Kopecky CM, Lechtzin N, Li Y, Lysinger J, Molina O, Nakamura C, Packer KA, Poch KR, Quittner AL, Radford P, Redway AJ, Sagel SD, Sprandel S, Taylor-Cousar JL, Vroom JB, Yoshikawa R, Clancy JP, Elborn JS, Olivier KN, Cox DR. BMC Med Res Methodol. 2019 Apr 26;19(1):88. doi: 10.1186/s12874-019-0705-0.

Randomization of Left-right Asymmetry and Congenital Heart Defects: The Role of DNAH5 in Humans and Mice. Nöthe-Menchen T, Wallmeier J, Pennekamp P, Höben IM, Olbrich H, Loges NT, Raidt J, Dougherty GW, Hjeij R, Dworniczak B, Omran H. Circ Genom Precis Med. 2019 Oct 22:10.1161/CIRCGEN.119.002686. doi: 10.1161/CIRCGEN.119.002686. Online ahead of print.

Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients. Morimoto K, Hijikata M, Zariwala MA, Nykamp K, Inaba A, Guo TC, Yamada H, Truty R, Sasaki Y, Ohta K, Kudoh S, Leigh MW, Knowles MR, Keicho N. Mol Genet Genomic Med. 2019 Aug;7(8):e838. doi: 10.1002/mgg3.838. Epub 2019 Jul 4.

Summary for Clinicians: Diagnosis of Primary Ciliary Dyskinesia. O'Connor MG, Griffiths A, Iyer NP, Shapiro AJ, Wilson KC, Thomson CC. Ann Am Thorac Soc. 2019 Feb;16(2):171-174. doi: 10.1513/AnnalsATS.201810-693CME.

The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia. Hannah WB, DeBrosse S, Kinghorn B, Strausbaugh S, Aitken ML, Rosenfeld M, Wolf WE, Knowles MR, Zariwala MA. Mol Genet Genomic Med. 2019 Sep;7(9):e911. doi: 10.1002/mgg3.911. Epub 2019 Aug 1.

Validation of pediatric health-related quality of life instruments for primary ciliary dyskinesia (QOL-PCD). Behan L, Leigh MW, Dell SD, Quittner AL, Hogg C, Lucas JS. Pediatr Pulmonol. 2019 Dec;54(12):2011-2020. doi: 10.1002/ppul.24507. Epub 2019 Sep 1.

Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications. Horani A, Ferkol TW. Chest. 2018 Sep;154(3):645-652. doi: 10.1016/j.chest.2018.05.007. Epub 2018 May 22.

Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline. Shapiro AJ, Davis SD, Polineni D, Manion M, Rosenfeld M, Dell SD, Chilvers MA, Ferkol TW, Zariwala MA, Sagel SD, Josephson M, Morgan L, Yilmaz O, Olivier KN, Milla C, Pittman JE, Daniels MLA, Jones MH, Janahi IA, Ware SM, Daniel SJ, Cooper ML, Nogee LM, Anton B, Eastvold T, Ehrne L, Guadagno E, Knowles MR, Leigh MW, Lavergne V; American Thoracic Society Assembly on Pediatrics. Am J Respir Crit Care Med. 2018 Jun 15;197(12):e24-e39. doi: 10.1164/rccm.201805-0819ST.

Establishment of the early cilia preassembly protein complex during motile ciliogenesis. Horani A, Ustione A, Huang T, Firth AL, Pan J, Gunsten SP, Haspel JA, Piston DW, Brody SL. Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1221-E1228. doi: 10.1073/pnas.1715915115. Epub 2018 Jan 22.

Primary ciliary dyskinesia: keep it on your radar. Rosenfeld M, Ostrowski LE, Zariwala MA. Thorax. 2018 Feb;73(2):101-102. doi: 10.1136/thoraxjnl-2017-210776. Epub 2017 Nov 13.

The Prevalence and Significance of Staphylococcus aureus in Patients with Non-Cystic Fibrosis Bronchiectasis. Metersky ML, Aksamit TR, Barker A, Choate R, Daley CL, Daniels LA, DiMango A, Eden E, Griffith D, Johnson M, Knowles M, O'Donnell AE, Olivier K, Salathe M, Thomashow B, Tino G, Turino G, Winthrop KL, Mannino D. Ann Am Thorac Soc. 2018 Mar;15(3):365-370. doi: 10.1513/AnnalsATS.201706-426OC.

The prevalence of the defining features of primary ciliary dyskinesia within a cri du chat syndrome cohort. Sanders CD, Leigh MW, Chao KC, Weck KE, King I, Wolf WE, Campbell DJ, Knowles MR, Zariwala MA, Shapiro AJ. Pediatr Pulmonol. 2018 Nov;53(11):1565-1573. doi: 10.1002/ppul.24159. Epub 2018 Sep 20.

A comparison of nasal nitric oxide measurement modes. Deschamp AR, Schornick L, Clem C, Hazucha M, Shapiro AJ, Davis SD. Pediatr Pulmonol. 2017 Nov;52(11):1381-1382. doi: 10.1002/ppul.23780. Epub 2017 Aug 16.

Accuracy of Nasal Nitric Oxide Measurement as a Diagnostic Test for Primary Ciliary Dyskinesia. A Systematic Review and Meta-analysis. Shapiro AJ, Josephson M, Rosenfeld M, Yilmaz O, Davis SD, Polineni D, Guadagno E, Leigh MW, Lavergne V. Ann Am Thorac Soc. 2017 Jul;14(7):1184-1196. doi: 10.1513/AnnalsATS.201701-062SR.

An Official American Thoracic Society Workshop Report: Translational Research in Rare Respiratory Diseases. Kristof AS, Petrof BJ, Hamid Q, Kolb M, Landry JS, MacKenzie A, McCormack FX, Murawski IJ, Moss J, Rauch F, Rosas IO, Shapiro AJ, Smith BM, Thomas DY, Trapnell BC, Young LR, Zariwala MA; ATS Assembly on Respiratory Cell and Molecular Biology. Ann Am Thorac Soc. 2017 Aug;14(8):1239-1247. doi: 10.1513/AnnalsATS.201705-406WS.

Cilia and Mucociliary Clearance. Bustamante-Marin XM, Ostrowski LE. Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4):a028241. doi: 10.1101/cshperspect.a028241.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, Dell S, Eber E, Escudier E, Hirst RA, Hogg C, Jorissen M, Latzin P, Legendre M, Leigh MW, Midulla F, Nielsen KG, Omran H, Papon JF, Pohunek P, Redfern B, Rigau D, Rindlisbacher B, Santamaria F, Shoemark A, Snijders D, Tonia T, Titieni A, Walker WT, Werner C, Bush A, Kuehni CE. Eur Respir J. 2017 Jan 4;49(1):1601090. doi: 10.1183/13993003.01090-2016. Print 2017 Jan.

Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort. Goutaki M, Halbeisen FS, Spycher BD, Maurer E, Belle F, Amirav I, Behan L, Boon M, Carr S, Casaulta C, Clement A, Crowley S, Dell S, Ferkol T, Haarman EG, Karadag B, Knowles M, Koerner-Rettberg C, Leigh MW, Loebinger MR, Mazurek H, Morgan L, Nielsen KG, Phillipsen M, Sagel SD, Santamaria F, Schwerk N, Yiallouros P, Lucas JS, Kuehni CE; PCD Israeli Consortium; Swiss PCD Group; French Reference Centre for Rare Lung Diseases. Eur Respir J. 2017 Dec 21;50(6):1701659. doi: 10.1183/13993003.01659-2017. Print 2017 Dec.

Primary ciliary dyskinesia: mechanisms and management. Damseh N, Quercia N, Rumman N, Dell SD, Kim RH. Appl Clin Genet. 2017 Sep 19;10:67-74. doi: 10.2147/TACG.S127129. eCollection 2017.

Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance. Blackburn K, Bustamante-Marin X, Yin W, Goshe MB, Ostrowski LE. J Proteome Res. 2017 Apr 7;16(4):1579-1592. doi: 10.1021/acs.jproteome.6b00972. Epub 2017 Mar 27.

Respiratory manifestations in 38 patients with Alström syndrome. Boerwinkle C, Marshall JD, Bryant J, Gahl WA, Olivier KN, Gunay-Aygun M. Pediatr Pulmonol. 2017 Apr;52(4):487-493. doi: 10.1002/ppul.23607. Epub 2016 Dec 28.

Validation of a health-related quality of life instrument for primary ciliary dyskinesia (QOL-PCD). Behan L, Leigh MW, Dell SD, Dunn Galvin A, Quittner AL, Lucas JS. Thorax. 2017 Sep;72(9):832-839. doi: 10.1136/thoraxjnl-2016-209356. Epub 2017 Feb 28.

Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure. Shapiro AJ, Leigh MW. Ultrastruct Pathol. 2017 Nov-Dec;41(6):373-385. doi: 10.1080/01913123.2017.1362088. Epub 2017 Sep 15.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents. Leigh MW, Ferkol TW, Davis SD, Lee HS, Rosenfeld M, Dell SD, Sagel SD, Milla C, Olivier KN, Sullivan KM, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer J, Hazucha MJ, Knowles MR. Ann Am Thorac Soc. 2016 Aug;13(8):1305-13. doi: 10.1513/AnnalsATS.201511-748OC.

Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Goutaki M, Meier AB, Halbeisen FS, Lucas JS, Dell SD, Maurer E, Casaulta C, Jurca M, Spycher BD, Kuehni CE. Eur Respir J. 2016 Oct;48(4):1081-1095. doi: 10.1183/13993003.00736-2016. Epub 2016 Aug 4.

Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD, Rosenfeld M, Olivier KN, Milla C, Daniel SJ, Kimple AJ, Manion M, Knowles MR, Leigh MW; Genetic Disorders of Mucociliary Clearance Consortium. Pediatr Pulmonol. 2016 Feb;51(2):115-32. doi: 10.1002/ppul.23304. Epub 2015 Sep 29.

Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants. Daniels ML, Birchard KR, Lowe JR, Patrone MV, Noone PG, Knowles MR. Ann Am Thorac Soc. 2016 Oct;13(10):1712-1720. doi: 10.1513/AnnalsATS.201603-161OC.

Genetics and biology of primary ciliary dyskinesia. Horani A, Ferkol TW, Dutcher SK, Brody SL. Paediatr Respir Rev. 2016 Mar;18:18-24. doi: 10.1016/j.prrv.2015.09.001. Epub 2015 Sep 11.

Primary Ciliary Dyskinesia. Knowles MR, Zariwala M, Leigh M. Clin Chest Med. 2016 Sep;37(3):449-61. doi: 10.1016/j.ccm.2016.04.008. Epub 2016 Jun 30.

Primary Ciliary Dyskinesia: First Health-related Quality-of-Life Measures for Pediatric Patients. Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL. Ann Am Thorac Soc. 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC.

Primary ciliary dyskinesia and associated sensory ciliopathies. Horani A, Ferkol TW. Expert Rev Respir Med. 2016;10(5):569-76. doi: 10.1586/17476348.2016.1165612. Epub 2016 Mar 28.

The evolving spectrum of ciliopathies and respiratory disease. Milla CE. Curr Opin Pediatr. 2016 Jun;28(3):339-47. doi: 10.1097/MOP.0000000000000358.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD. Lucas JS, Behan L, Dunn Galvin A, Alpern A, Morris AM, Carroll MP, Knowles MR, Leigh MW, Quittner AL. Eur Respir J. 2015 Aug;46(2):375-83. doi: 10.1183/09031936.00216214. Epub 2015 May 14.

Carrier frequencies of eleven mutations in eight genes associated with primary ciliary dyskinesia in the Ashkenazi Jewish population. Fedick AM, Jalas C, Treff NR, Knowles MR, Zariwala MA. Mol Genet Genomic Med. 2015 Mar;3(2):137-42. doi: 10.1002/mgg3.124. Epub 2014 Dec 6.

Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Davis SD, Ferkol TW, Rosenfeld M, Lee HS, Dell SD, Sagel SD, Milla C, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer JP, Hazucha MJ, Cooper ML, Knowles MR, Leigh MW. Am J Respir Crit Care Med. 2015 Feb 1;191(3):316-24. doi: 10.1164/rccm.201409-1672OC.

Genetics, diagnosis, and future treatment strategies for primary ciliary dyskinesia. Daniels ML, Noone PG. Expert Opin Orphan Drugs. 2015 Mar 1;3(1):31-44. doi: 10.1517/21678707.2015.989212. Epub 2014 Nov 29.

Primary ciliary dyskinesia. Lobo J, Zariwala MA, Noone PG. Semin Respir Crit Care Med. 2015 Apr;36(2):169-79. doi: 10.1055/s-0035-1546748. Epub 2015 Mar 31.

Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease. Szymanski EP, Leung JM, Fowler CJ, Haney C, Hsu AP, Chen F, Duggal P, Oler AJ, McCormack R, Podack E, Drummond RA, Lionakis MS, Browne SK, Prevots DR, Knowles M, Cutting G, Liu X, Devine SE, Fraser CM, Tettelin H, Olivier KN, Holland SM. Am J Respir Crit Care Med. 2015 Sep 1;192(5):618-28. doi: 10.1164/rccm.201502-0387OC.

Standardization and validation of a novel and simple method to assess lumbar dural sac size. Daniels ML, Lowe JR, Roy P, Patrone MV, Conyers JM, Fine JP, Knowles MR, Birchard KR. Clin Radiol. 2015 Feb;70(2):146-52. doi: 10.1016/j.crad.2014.10.009. Epub 2014 Nov 27.

The Evolution of Cystic Fibrosis Care. Pittman JE, Ferkol TW. Chest. 2015 Aug;148(2):533-542. doi: 10.1378/chest.14-1997.

The prevalence of clinical features associated with primary ciliary dyskinesia in a heterotaxy population: results of a web-based survey. Shapiro AJ, Tolleson-Rinehart S, Zariwala MA, Knowles MR, Leigh MW. Cardiol Young. 2015 Apr;25(4):752-9. doi: 10.1017/S1047951114000912. Epub 2014 Jun 6.

Whole-Exome Sequencing and Targeted Copy Number Analysis in Primary Ciliary Dyskinesia. Marshall CR, Scherer SW, Zariwala MA, Lau L, Paton TA, Stockley T, Jobling RK, Ray PN, Knowles MR; FORGE Canada Consortium, Hall DA, Dell SD, Kim RH. G3 (Bethesda). 2015 Jul 2;5(8):1775-81. doi: 10.1534/g3.115.019851.

A new tool improves diagnostic test performance for transmission em evaluation of axonemal dynein arms. Funkhouser WK 3rd, Niethammer M, Carson JL, Burns KA, Knowles MR, Leigh MW, Zariwala MA, Funkhouser WK Jr. Ultrastruct Pathol. 2014 Aug;38(4):248-55. doi: 10.3109/01913123.2013.815081. Epub 2013 Aug 19.

Cri du chat syndrome and primary ciliary dyskinesia: a common genetic cause on chromosome 5p. Shapiro AJ, Weck KE, Chao KC, Rosenfeld M, Nygren AO, Knowles MR, Leigh MW, Zariwala MA. J Pediatr. 2014 Oct;165(4):858-61. doi: 10.1016/j.jpeds.2014.06.048. Epub 2014 Jul 25.

Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia. Lin J, Yin W, Smith MC, Song K, Leigh MW, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. Nat Commun. 2014 Dec 4;5:5727. doi: 10.1038/ncomms6727.

Environmental risks for nontuberculous mycobacteria. Individual exposures and climatic factors in the cystic fibrosis population. Prevots DR, Adjemian J, Fernandez AG, Knowles MR, Olivier KN. Ann Am Thorac Soc. 2014 Sep;11(7):1032-8. doi: 10.1513/AnnalsATS.201404-184OC.

Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy. Shapiro AJ, Davis SD, Ferkol T, Dell SD, Rosenfeld M, Olivier KN, Sagel SD, Milla C, Zariwala MA, Wolf W, Carson JL, Hazucha MJ, Burns K, Robinson B, Knowles MR, Leigh MW; Genetic Disorders of Mucociliary Clearance Consortium. Chest. 2014 Nov;146(5):1176-1186. doi: 10.1378/chest.13-1704.

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype. Knowles MR, Ostrowski LE, Leigh MW, Sears PR, Davis SD, Wolf WE, Hazucha MJ, Carson JL, Olivier KN, Sagel SD, Rosenfeld M, Ferkol TW, Dell SD, Milla CE, Randell SH, Yin W, Sannuti A, Metjian HM, Noone PG, Noone PJ, Olson CA, Patrone MV, Dang H, Lee HS, Hurd TW, Gee HY, Otto EA, Halbritter J, Kohl S, Kircher M, Krischer J, Bamshad MJ, Nickerson DA, Hildebrandt F, Shendure J, Zariwala MA. Am J Respir Crit Care Med. 2014 Mar 15;189(6):707-17. doi: 10.1164/rccm.201311-2047OC.

Picking up speed: advances in the genetics of primary ciliary dyskinesia. Horani A, Brody SL, Ferkol TW. Pediatr Res. 2014 Jan;75(1-2):158-64. doi: 10.1038/pr.2013.200. Epub 2013 Nov 5.

Primary ciliary dyskinesia and neonatal respiratory distress. Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S. Pediatrics. 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808.

Sperm-associated antigen 6 (SPAG6) deficiency and defects in ciliogenesis and cilia function: polarity, density, and beat. Teves ME, Sears PR, Li W, Zhang Z, Tang W, van Reesema L, Costanzo RM, Davis CW, Knowles MR, Strauss JF 3rd, Zhang Z. PLoS One. 2014 Oct 21;9(10):e107271. doi: 10.1371/journal.pone.0107271. eCollection 2014.

The role of molecular genetic analysis in the diagnosis of primary ciliary dyskinesia. Kim RH, A Hall D, Cutz E, Knowles MR, Nelligan KA, Nykamp K, Zariwala MA, Dell SD. Ann Am Thorac Soc. 2014 Mar;11(3):351-9. doi: 10.1513/AnnalsATS.201306-194OC.

ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. Hjeij R, Lindstrand A, Francis R, Zariwala MA, Liu X, Li Y, Damerla R, Dougherty GW, Abouhamed M, Olbrich H, Loges NT, Pennekamp P, Davis EE, Carvalho CM, Pehlivan D, Werner C, Raidt J, Köhler G, Häffner K, Reyes-Mugica M, Lupski JR, Leigh MW, Rosenfeld M, Morgan LC, Knowles MR, Lo CW, Katsanis N, Omran H. Am J Hum Genet. 2013 Aug 8;93(2):357-67. doi: 10.1016/j.ajhg.2013.06.009. Epub 2013 Jul 11.

Abnormal nasal nitric oxide production, ciliary beat frequency, and Toll-like receptor response in pulmonary nontuberculous mycobacterial disease epithelium. Fowler CJ, Olivier KN, Leung JM, Smith CC, Huth AG, Root H, Kuhns DB, Logun C, Zelazny A, Frein CA, Daub J, Haney C, Shelhamer JH, Bryant CE, Holland SM. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1374-81. doi: 10.1164/rccm.201212-2197OC.

DYX1C1 is required for axonemal dynein assembly and ciliary motility. Tarkar A, Loges NT, Slagle CE, Francis R, Dougherty GW, Tamayo JV, Shook B, Cantino M, Schwartz D, Jahnke C, Olbrich H, Werner C, Raidt J, Pennekamp P, Abouhamed M, Hjeij R, Köhler G, Griese M, Li Y, Lemke K, Klena N, Liu X, Gabriel G, Tobita K, Jaspers M, Morgan LC, Shapiro AJ, Letteboer SJ, Mans DA, Carson JL, Leigh MW, Wolf WE, Chen S, Lucas JS, Onoufriadis A, Plagnol V, Schmidts M, Boldt K; UK10K, Roepman R, Zariwala MA, Lo CW, Mitchison HM, Knowles MR, Burdine RD, Loturco JJ, Omran H. Nat Genet. 2013 Sep;45(9):995-1003. doi: 10.1038/ng.2707. Epub 2013 Jul 21.

Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia. Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, Yin W, Berg JS, Davis SD, Dell SD, Ferkol TW, Rosenfeld M, Sagel SD, Milla CE, Olivier KN, Turner EH, Lewis AP, Bamshad MJ, Nickerson DA, Shendure J, Zariwala MA; Genetic Disorders of Mucociliary Clearance Consortium. Am J Hum Genet. 2013 Jan 10;92(1):99-106. doi: 10.1016/j.ajhg.2012.11.003. Epub 2012 Dec 20.

Founder mutation in RSPH4A identified in patients of Hispanic descent with primary ciliary dyskinesia. Daniels ML, Leigh MW, Davis SD, Armstrong MC, Carson JL, Hazucha M, Dell SD, Eriksson M, Collins FS, Knowles MR, Zariwala MA. Hum Mutat. 2013 Oct;34(10):1352-6. doi: 10.1002/humu.22371. Epub 2013 Aug 6.

Human airway ciliary dynamics. Sears PR, Thompson K, Knowles MR, Davis CW. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;304(3):L170-83. doi: 10.1152/ajplung.00105.2012. Epub 2012 Nov 9.

Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, Wilson R, Taylor-Cox T, Dewar A, Jackson C, Goggin P, Loges NT, Olbrich H, Jaspers M, Jorissen M, Leigh MW, Wolf WE, Daniels ML, Noone PG, Ferkol TW, Sagel SD, Rosenfeld M, Rutman A, Dixit A, O'Callaghan C, Lucas JS, Hogg C, Scambler PJ, Emes RD; Uk10k, Chung EM, Shoemark A, Knowles MR, Omran H, Mitchison HM. Hum Mutat. 2013 Mar;34(3):462-72. doi: 10.1002/humu.22261. Epub 2013 Feb 11.

Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms. Knowles MR, Ostrowski LE, Loges NT, Hurd T, Leigh MW, Huang L, Wolf WE, Carson JL, Hazucha MJ, Yin W, Davis SD, Dell SD, Ferkol TW, Sagel SD, Olivier KN, Jahnke C, Olbrich H, Werner C, Raidt J, Wallmeier J, Pennekamp P, Dougherty GW, Hjeij R, Gee HY, Otto EA, Halbritter J, Chaki M, Diaz KA, Braun DA, Porath JD, Schueler M, Baktai G, Griese M, Turner EH, Lewis AP, Bamshad MJ, Nickerson DA, Hildebrandt F, Shendure J, Omran H, Zariwala MA. Am J Hum Genet. 2013 Oct 3;93(4):711-20. doi: 10.1016/j.ajhg.2013.07.025. Epub 2013 Sep 19.

Primary ciliary dyskinesia-causing mutations in Amish and Mennonite communities. Ferkol TW, Puffenberger EG, Lie H, Helms C, Strauss KA, Bowcock A, Carson JL, Hazucha M, Morton DH, Patel AC, Leigh MW, Knowles MR, Zariwala MA. J Pediatr. 2013 Aug;163(2):383-7. doi: 10.1016/j.jpeds.2013.01.061. Epub 2013 Mar 7.

Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Am J Respir Crit Care Med. 2013 Oct 15;188(8):913-22. doi: 10.1164/rccm.201301-0059CI.

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, Lavange LM, Horton BJ, Qaqish B, Carson JL, Davis SD, Dell SD, Ferkol TW, Atkinson JJ, Olivier KN, Sagel SD, Rosenfeld M, Milla C, Lee HS, Krischer J, Zariwala MA, Knowles MR. Ann Am Thorac Soc. 2013 Dec;10(6):574-81. doi: 10.1513/AnnalsATS.201305-110OC.

ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. Zariwala MA, Gee HY, Kurkowiak M, Al-Mutairi DA, Leigh MW, Hurd TW, Hjeij R, Dell SD, Chaki M, Dougherty GW, Adan M, Spear PC, Esteve-Rudd J, Loges NT, Rosenfeld M, Diaz KA, Olbrich H, Wolf WE, Sheridan E, Batten TF, Halbritter J, Porath JD, Kohl S, Lovric S, Hwang DY, Pittman JE, Burns KA, Ferkol TW, Sagel SD, Olivier KN, Morgan LC, Werner C, Raidt J, Pennekamp P, Sun Z, Zhou W, Airik R, Natarajan S, Allen SJ, Amirav I, Wieczorek D, Landwehr K, Nielsen K, Schwerk N, Sertic J, Köhler G, Washburn J, Levy S, Fan S, Koerner-Rettberg C, Amselem S, Williams DS, Mitchell BJ, Drummond IA, Otto EA, Omran H, Knowles MR, Hildebrandt F. Am J Hum Genet. 2013 Aug 8;93(2):336-45. doi: 10.1016/j.ajhg.2013.06.007. Epub 2013 Jul 25.

Ciliopathies: the central role of cilia in a spectrum of pediatric disorders. Ferkol TW, Leigh MW. J Pediatr. 2012 Mar;160(3):366-71. doi: 10.1016/j.jpeds.2011.11.024. Epub 2011 Dec 16.

Cutting edge genetic studies in primary ciliary dyskinesia. Knowles MR, Leigh MW, Zariwala MA. Thorax. 2012 May;67(5):464; author reply 464. doi: 10.1136/thoraxjnl-2012-201609. Epub 2012 Feb 10.

High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Nakhleh N, Francis R, Giese RA, Tian X, Li Y, Zariwala MA, Yagi H, Khalifa O, Kureshi S, Chatterjee B, Sabol SL, Swisher M, Connelly PS, Daniels MP, Srinivasan A, Kuehl K, Kravitz N, Burns K, Sami I, Omran H, Barmada M, Olivier K, Chawla KK, Leigh M, Jonas R, Knowles M, Leatherbury L, Lo CW. Circulation. 2012 May 8;125(18):2232-42. doi: 10.1161/CIRCULATIONAHA.111.079780. Epub 2012 Apr 12.

Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Knowles MR, Leigh MW, Carson JL, Davis SD, Dell SD, Ferkol TW, Olivier KN, Sagel SD, Rosenfeld M, Burns KA, Minnix SL, Armstrong MC, Lori A, Hazucha MJ, Loges NT, Olbrich H, Becker-Heck A, Schmidts M, Werner C, Omran H, Zariwala MA; Genetic Disorders of Mucociliary Clearance Consortium. Thorax. 2012 May;67(5):433-41. doi: 10.1136/thoraxjnl-2011-200301. Epub 2011 Dec 18.

Whole-exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. Horani A, Druley TE, Zariwala MA, Patel AC, Levinson BT, Van Arendonk LG, Thornton KC, Giacalone JC, Albee AJ, Wilson KS, Turner EH, Nickerson DA, Shendure J, Bayly PV, Leigh MW, Knowles MR, Brody SL, Dutcher SK, Ferkol TW. Am J Hum Genet. 2012 Oct 5;91(4):685-93. doi: 10.1016/j.ajhg.2012.08.022.

Diagnostic yield of nasal scrape biopsies in primary ciliary dyskinesia: a multicenter experience. Olin JT, Burns K, Carson JL, Metjian H, Atkinson JJ, Davis SD, Dell SD, Ferkol TW, Milla CE, Olivier KN, Rosenfeld M, Baker B, Leigh MW, Knowles MR, Sagel SD; Genetic Disorders of Mucociliary Clearance Consortium. Pediatr Pulmonol. 2011 May;46(5):483-8. doi: 10.1002/ppul.21402. Epub 2011 Jan 31.

Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: implications for application to clinical testing. Berg JS, Evans JP, Leigh MW, Omran H, Bizon C, Mane K, Knowles MR, Weck KE, Zariwala MA. Genet Med. 2011 Mar;13(3):218-29. doi: 10.1097/GIM.0b013e318203cff2.

The challenges of diagnosing primary ciliary dyskinesia. Leigh MW, O'Callaghan C, Knowles MR. Proc Am Thorac Soc. 2011 Sep;8(5):434-7. doi: 10.1513/pats.201103-028SD.

The emerging genetics of primary ciliary dyskinesia. Zariwala MA, Omran H, Ferkol TW. Proc Am Thorac Soc. 2011 Sep;8(5):430-3. doi: 10.1513/pats.201103-023SD.

Update of respiratory tract disease in children with primary ciliary dyskinesia. Sagel SD, Davis SD, Campisi P, Dell SD. Proc Am Thorac Soc. 2011 Sep;8(5):438-43. doi: 10.1513/pats.201103-024SD.

Primary ciliary dyskinesia in Amish communities. Lie H, Zariwala MA, Helms C, Bowcock AM, Carson JL, Brown DE 3rd, Hazucha MJ, Forsen J, Molter D, Knowles MR, Leigh MW, Ferkol TW. J Pediatr. 2010 Jun;156(6):1023-1025. doi: 10.1016/j.jpeds.2010.01.054. Epub 2010 Mar 29.

Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA. Genet Med. 2009 Jul;11(7):473-87. doi: 10.1097/GIM.0b013e3181a53562.

Clinical research for rare disease: opportunities, challenges, and solutions. Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA; Rare Diseases Clinical Research Network. Mol Genet Metab. 2009 Jan;96(1):20-6. doi: 10.1016/j.ymgme.2008.10.003. Epub 2008 Nov 13.

Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Loges NT, Olbrich H, Becker-Heck A, Häffner K, Heer A, Reinhard C, Schmidts M, Kispert A, Zariwala MA, Leigh MW, Knowles MR, Zentgraf H, Seithe H, Nürnberg G, Nürnberg P, Reinhardt R, Omran H. Am J Hum Genet. 2009 Dec;85(6):883-9. doi: 10.1016/j.ajhg.2009.10.018.

Primary ciliary dyskinesia: improving the diagnostic approach. Leigh MW, Zariwala MA, Knowles MR. Curr Opin Pediatr. 2009 Jun;21(3):320-5. doi: 10.1097/MOP.0b013e328329cddb.

Early lung disease in young children with primary ciliary dyskinesia. Brown DE, Pittman JE, Leigh MW, Fordham L, Davis SD. Pediatr Pulmonol. 2008 May;43(5):514-6. doi: 10.1002/ppul.20792.

A heterozygous mutation disrupting the SPAG16 gene results in biochemical instability of central apparatus components of the human sperm axoneme. Zhang Z, Zariwala MA, Mahadevan MM, Caballero-Campo P, Shen X, Escudier E, Duriez B, Bridoux AM, Leigh M, Gerton GL, Kennedy M, Amselem S, Knowles MR, Strauss JF 3rd. Biol Reprod. 2007 Nov;77(5):864-71. doi: 10.1095/biolreprod.107.063206. Epub 2007 Aug 15.

Burkholderia gladioli: five year experience in a cystic fibrosis and lung transplantation center. Kennedy MP, Coakley RD, Donaldson SH, Aris RM, Hohneker K, Wedd JP, Knowles MR, Gilligan PH, Yankaskas JR. J Cyst Fibros. 2007 Jul;6(4):267-73. doi: 10.1016/j.jcf.2006.10.007. Epub 2006 Nov 29.

Calcium stone lithoptysis in primary ciliary dyskinesia. Kennedy MP, Noone PG, Carson J, Molina PL, Ghio A, Zariwala MA, Minnix SL, Knowles MR. Respir Med. 2007 Jan;101(1):76-83. doi: 10.1016/j.rmed.2006.04.007. Epub 2006 Jun 6.

Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, Robinson BV, Minnix SL, Olbrich H, Severin T, Ahrens P, Lange L, Morillas HN, Noone PG, Zariwala MA, Knowles MR. Circulation. 2007 Jun 5;115(22):2814-21. doi: 10.1161/CIRCULATIONAHA.106.649038. Epub 2007 May 21.

Genetic defects in ciliary structure and function. Zariwala MA, Knowles MR, Omran H. Annu Rev Physiol. 2007;69:423-50. doi: 10.1146/annurev.physiol.69.040705.141301.

High-resolution CT of patients with primary ciliary dyskinesia. Kennedy MP, Noone PG, Leigh MW, Zariwala MA, Minnix SL, Knowles MR, Molina PL. AJR Am J Roentgenol. 2007 May;188(5):1232-8. doi: 10.2214/AJR.06.0965.

Primary ciliary dyskinesia: recent advances in pathogenesis, diagnosis and treatment. Lie H, Ferkol T. Drugs. 2007;67(13):1883-92. doi: 10.2165/00003495-200767130-00006.

Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Zariwala MA, Leigh MW, Ceppa F, Kennedy MP, Noone PG, Carson JL, Hazucha MJ, Lori A, Horvath J, Olbrich H, Loges NT, Bridoux AM, Pennarun G, Duriez B, Escudier E, Mitchison HM, Chodhari R, Chung EM, Morgan LC, de Iongh RU, Rutland J, Pradal U, Omran H, Amselem S, Knowles MR. Am J Respir Crit Care Med. 2006 Oct 15;174(8):858-66. doi: 10.1164/rccm.200603-370OC. Epub 2006 Jul 20.

Primary ciliary dyskinesia and newborn respiratory distress. Ferkol T, Leigh M. Semin Perinatol. 2006 Dec;30(6):335-40. doi: 10.1053/j.semperi.2005.11.001.

Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Sheridan MB, Fong P, Groman JD, Conrad C, Flume P, Diaz R, Harris C, Knowles M, Cutting GR. Hum Mol Genet. 2005 Nov 15;14(22):3493-8. doi: 10.1093/hmg/ddi374. Epub 2005 Oct 5.

Biochemical signatures of disease severity in multiple sulfatase deficiency. Adang LA, Mowafy S, Herbst ZM, Zhou Z, Schlotawa L, Radhakrishnan K, Bentley B, Pham V, Yu E, Pillai NR, Orchard PJ, De Castro M, Vanderver A, Pasquali M, Gelb MH, Ahrens-Nicklas RC. J Inherit Metab Dis. 2023 Oct 23. doi: 10.1002/jimd.12688. Online ahead of print.

Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C. Mirchi A, Guay SP, Tran LT, Wolf NI, Vanderver A, Brais B, Sylvain M, Pohl D, Rossignol E, Saito M, Moutton S, González-Gutiérrez-Solana L, Thiffault I, Kruer MC, Moron DG, Kauffman M, Goizet C, Sztriha L, Glamuzina E, Melançon SB, Naidu S, Retrouvey JM, Lacombe S, Bernardino-Cuesta B, De Bie I, Bernard G. J Med Genet. 2023 Oct;60(10):1026-1034. doi: 10.1136/jmg-2023-109223. Epub 2023 May 16. PMID: 37197783

RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is a rare genetic disorder characterized by hypomyelination (inability to produce sufficient myelin, the fatty coating surrounding nerve fibers, at normal levels during development), neurological dysfunction, hypodontia (missing teeth), and hypogonadotropic hypogonadism (delayed puberty). Description of craniofacial features in individuals with POLR3-HLD is currently very limited.

In this study, researchers assessed the craniofacial features of 31 patients with POLR3-HLD. The team also proposed genotype-phenotype correlations based on patients’ facial features.

Results demonstrate that craniofacial abnormalities are common in patients with POLR3-HLD. Authors note that these findings will assist clinicians in diagnosing POLR3-HLD, help to provide care directed to this patient population’s specific needs, and allow future studies characterizing the underlying pathophysiology. 

Early Detection of Adrenal Insufficiency: The Impact of Newborn Screening for Adrenoleukodystrophy. Ramirez Alcantara J, Grant NR, Sethuram S, Nagy A, Becker C, Sahai I, Stanley T, Halper A, Eichler FS. J Clin Endocrinol Metab. 2023 Oct 18;108(11):e1306-e1315.

Adrenoleukodystrophy (ALD) is an X-linked disorder (on the X chromosome) characterized by accumulation of very long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Males with ALD have a high risk of developing adrenal insufficiency, which can be life-threatening when undetected. Although newborn screening for ALD is becoming more common, its impact on clinical management has not yet been reported.

In this study, researchers investigated the impact of newborn screening on time to diagnosis of adrenal insufficiency in children with ALD. The team conducted a medical chart review of 116 patients with ALD, extracting information about diagnosis in all patients and adrenal insufficiency surveillance, diagnosis, and treatment in boys with ALD.

Results suggest that implementing newborn screening for ALD leads to significantly earlier detection of adrenal insufficiency, as well as earlier initiation of glucocorticoid supplementation in boys affected by ALD.

Exploration of Gross Motor Function in Aicardi-Goutières Syndrome. Gavazzi F, Glanzman AM, Woidill S, Formanowski B, Dixit A, Isaacs D, Kornafel T, Ballance E, Pierce SR, Modesti N, Barcelos I, Cusack SV, Jan AK, Flores Z, Sherbini O, Vincent A, D'Aiello R, Lorch SA, DeMauro SB, Jawad A, Vanderver A, Adang L. J Child Neurol. 2023 Jul 27:8830738231188753. doi: 10.1177/08830738231188753. Epub ahead of print. PMID: 37499181

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. The AGS Severity Scale is used to measure outcomes in individuals with AGS. However, because of the relatively limited granularity of this tool, there is a need to define tools that can measure function across the AGS spectrum. 

In this study, researchers explored gross motor function as an outcome measure of AGS. The team administered the Gross Motor Function Measure–88 (GMFM-88) and AGS Severity Scale in 71 individuals affected by AGS, characterizing performance variability by genotype. 

Results support the GMFM-88 as a potential clinical outcome assessment in subsets of the AGS population. Authors note the need for additional validation of outcome measures that can reflect the diverse gross motor function observed in individuals with AGS, including low motor function.

Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A. Gavazzi F, Patel V, Charsar B, Glanzman A, Erler J, Sevagamoorthy A, McKenzie E, Kornafel T, Ballance E, Pierce SR, Teng M, Formanowski B, Woidill S, Shults J, Wassmer E, Tonduti D, Magrinelli F, Bernard G, Van Der Knaap M, Wolf N, Adang L, Vanderver A. J Child Neurol. 2023 Aug;38(8-9):498-504. doi: 10.1177/08830738231188159. Epub 2023 Jul 17.

Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy. Al-Saady M, Beerepoot S, Plug BC, Breur M, Galabova H, Pouwels PJW, Boelens JJ, Lindemans C, van Hasselt PM, Matzner U, Vanderver A, Bugiani M, van der Knaap MS, Wolf NI. Ann Clin Transl Neurol. 2023 Jul;10(7):1146-1159. doi: 10.1002/acn3.51796. Epub 2023 May 22.

Role of Basal Forebrain Neurons in Adrenomyeloneuropathy in Mice and Humans. Gong Y, Laheji F, Berenson A, Li Y, Moser A, Qian A, Frosch M, Sadjadi R, Hahn R, Maguire CA, Eichler F. Ann Neurol. 2023 Dec 7. doi: 10.1002/ana.26849. Online ahead of print.

SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia. Srivastava S, Shaked HM, Gable K, Gupta SD, Pan X, Somashekarappa N, Han G, Mohassel P, Gotkine M, Doney E, Goldenberg P, Tan QKG, Gong Y, Kleinstiver B, Wishart B, Cope H, Pires CB, Stutzman H, Spillmann RC; Undiagnosed Disease Network; Sadjadi R, Elpeleg O, Lee CH, Bellen HJ, Edvardson S, Eichler F, Dunn TM. Brain. 2023 Jan 30:awac460. doi: 10.1093/brain/awac460. Epub ahead of print. PMID: 36718090.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders that primarily affect the upper motor neurons. In the nervous system, a diverse family of lipids called sphingolipids play a critical role in structural and signaling functions. The synthesis of sphingolipids is regulated by the protein SPTSSA.

In this study, researchers identified three children with a complex form of HSP. The team used exome sequencing to discover two different disease-causing variants in the SPTSSA gene. Next, they investigated the effects of these variants on sphingolipid synthesis.

Findings showed that the variants in SPTSSA caused excessive sphingolipid synthesis, leading to HSP. Authors note that these findings provide a better understanding of the elevated sphingolipid synthesis involved in progressive neurodegenerative diseases.

Early-Onset Vascular Leukoencephalopathy Caused by Bi-Allelic NOTCH3 Variants. Stellingwerff MD, Nulton C, Helman G, Roosendaal SD, Benko WS, Pizzino A, Bugiani M, Vanderver A, Simons C, van der Knaap MS. Neuropediatrics. 2022 Apr;53(2):115-121. doi: 10.1055/a-1739-2722. Epub 2022 Jan 13. PMID: 35026854.

Cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease of the blood vessels that occurs when the thickening of blood vessel walls blocks the flow of blood to the brain. Heterozygous variants of the NOTCH3 gene are known to cause CADASIL, with patients typically presenting in adulthood. In this study, researchers describe three patients from two unrelated families presenting at an early age with a vascular leukoencephalopathy. The team reviewed clinical records, MRI, and CT scans of the patients. Genome sequencing revealed bi-allelic variants in the NOTCH3 gene. These results indicate that bi-allelic loss-of-function NOTCH3 variants may cause a vascular leukoencephalopathy, distinct from CADASIL.

Functional analysis of missense DARS2 variants in siblings with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Wongkittichote P, Magistrati M, Shimony JS, Smyser CD, Fatemi SA, Fine AS, Bellacchio E, Dallabona C, Shinawi M. Mol Genet Metab. 2022 Aug;136(4):260-267. doi: 10.1016/j.ymgme.2022.07.002. Epub 2022 Jul 5.

Hematologic abnormalities in Aicardi Goutières Syndrome. Adang LA, Gavazzi F, D'Aiello R, Isaacs D, Bronner N, Arici ZS, Flores Z, Jan A, Scher C, Sherbini O, Behrens EM, Goldbach-Mansky R, Olson TS, Lambert MP, Sullivan KE, Teachey DT, Witmer C, Vanderver A, Shults J. Mol Genet Metab. 2022 Jun 16:S1096-7192(22)00339-0. doi: 10.1016/j.ymgme.2022.06.003. Epub ahead of print. PMID: 35786528.

Aicardi Goutières syndrome (AGS) is an inherited disease that is associated with early onset neurologic disability and systemic inflammation. Cytopenias—conditions in which there are lower-than-normal numbers of blood cells—are a potentially serious, but poorly understood, complication of AGS. As new treatment options are developed, it is important to understand the roles of the disease versus the treatment in hematologic abnormalities, allowing for better management of cytopenia. In this study, researchers identified novel patterns of hematologic abnormalities in AGS. The team collected laboratory data throughout the lifespan from 142 individuals with AGS. Results showed that AGS results in multilineage cytopenias not limited to the neonatal period. Neutropenia, anemia, and thrombocytopenia were common. For patients on the treatment baricitinib, moderate to severe graded events of neutropenia, anemia, and leukopenia were more common, but rarely of clinical consequence. Based on these results, authors recommend careful monitoring of hematologic parameters in children with AGS throughout the lifespan, especially while on therapy. Authors also note that AGS should be considered in children with neurologic impairment of unclear cause and hematologic abnormalities.

Hospitalization Burden and Incidence of Krabbe Disease. Ghabash G, Wilkes J, Barney BJ, Bonkowsky JL. J Child Neurol. 2022 Jan;37(1):12-19. doi: 10.1177/08830738211027717. Epub 2021 Oct 20.

Identification of PMD subgroups using a myelination score for PMD. Harting I, Garbade SF, Rosendaal SD, Mohr A, Sherbini O, Vanderver A, Wolf NI. Eur J Paediatr Neurol. 2022 Nov;41:71-79. doi: 10.1016/j.ejpn.2022.10.003. Epub 2022 Nov 4.

Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration. Macintosh J, Derksen A, Poulin C, Braverman N, Vanderver A, Thiffault I, Albrecht S, Bernard G. Neurogenetics. 2022 Apr;23(2):151-156. doi: 10.1007/s10048-022-00683-8. Epub 2022 Jan 31. PMID: 35099671.

The protein NRROS (negative regulator of reactive oxygen species) is expressed by microglia (immune cells of the central nervous system) and perivascular macrophages (brain macrophages, or immune cells, characterized by a close association with the cerebral vasculature). To date, 9 individuals have been reported with biallelic (affecting both alleles of a gene) NRROS variants. In this study, researchers used exome sequencing to identify 2 novel NRROS variants—a missense variant and a premature stop codon—in an individual with a severe neurodegenerative phenotype. Through pathological examination, they found both extensive grey and white matter involvement, dystrophic calcifications, and infiltration of foamy macrophages. Authors state that this is the first reported case of NRROS variants with a mitochondrial ultrastructure abnormality noted on electron microscopy analysis of post-mortem tissue.

Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy: Timing and Treatment. Mallack EJ, Van Haren KP, Torrey A, van de Stadt S, Engelen M, Raymond GV, Fatemi A, Eichler FS. Neurology. 2022 May 24:10.1212/WNL.0000000000200571. doi: 10.1212/WNL.0000000000200571. Online ahead of print.

Psychometric outcome measures in beta-propeller protein-associated neurodegeneration (BPAN). Gavazzi F, Pierce SR, Vithayathil J, Cunningham K, Anderson K, McCann J, Moll A, Muirhead K, Sherbini O, Prange E, Dubbs H, Tochen L, Fraser J, Helbig I, Lewin N, Thakur N, Adang LA. Mol Genet Metab. 2022 Sep-Oct;137(1-2):26-32. doi: 10.1016/j.ymgme.2022.07.009. Epub 2022 Jul 20.

Restless Legs Syndrome in X-linked adrenoleukodystrophy. Winkelman JW, Grant NR, Molay F, Stephen CD, Sadjadi R, Eichler FS. Sleep Med. 2022 Mar;91:31-34. doi: 10.1016/j.sleep.2022.02.008. Epub 2022 Feb 16. PMID: 35245789; PMCID: PMC9035065.

X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease that causes progressive gait and balance problems. Leg discomfort, sleep disturbances, and pain contribute to daily disability. In this study, researchers investigated the prevalence and severity of restless legs syndrome (RLS) in 32 adults with ALD. The team gathered data from questionnaires, telephone interviews, neurological examinations, functional gait measures, and laboratory assessments. Results suggest a high prevalence of RLS in adults with ALD. Researchers also found that ALD patients with RLS have more neurological signs and symptoms, and RLS is more common in females with ALD than in males. Authors note that increased awareness of RLS in patients with ALD would allow for more effective treatment.

Sensorimotor outcomes in adrenomyeloneuropathy show significant disease progression. Keller JL, Eloyan A, Raymond GV, Fatemi A, Zackowski KM. J Inherit Metab Dis. 2022 Mar;45(2):308-317. doi: 10.1002/jimd.12457. Epub 2021 Dec 9. PMID: 34796974; PMCID: PMC8987487.

Adrenomyeloneuropathy is an X-linked disorder (on the X chromosome) characterized by the disruption in fat metabolism (break down) which leads to the accumulation of very long-chain fatty acids throughout the nervous system, adrenal glands, and testes. As current outcomes used to evaluate the disorder are limited, quantitative outcomes are needed. In this prospective study, researchers aimed to track sensorimotor outcomes in adults with adrenomyeloneuropathy and evaluate differences in progression between men and women. The team analyzed data to detect changes in outcomes over 2 years. Outcomes included postural sway in four static standing conditions, great-toe vibration, hip strength, walking velocity, timed up-and-go, and 6-minute walk distance. They found that participants showed significant worsening in all standing conditions, sensation, and strength. However, they showed more stability in walking, with only velocity significantly declining. For each sex, postural sway declined significantly in all conditions except for eyes closed feet together for women. Strength declined significantly by sex for hip flexion. Sex-specific significant decline was seen in walking for men only. Authors note that quantitative measures of postural sway, sensation strength, and walking are effective measures of adrenomyeloneuropathy progression in 2 years.

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS. Cetin Gedik K, Lamot L, Romano M, Demirkaya E, Piskin D, Torreggiani S, Adang LA, Armangue T, Barchus K, Cordova DR, Crow YJ, Dale RC, Durrant KL, Eleftheriou D, Fazzi EM, Gattorno M, Gavazzi F, Hanson EP, Lee-Kirsch MA, Montealegre Sanchez GA, Neven B, Orcesi S, Ozen S, Poli MC, Schumacher E, Tonduti D, Uss K, Aletaha D, Feldman BM, Vanderver A, Brogan PA, Goldbach-Mansky R. Ann Rheum Dis. 2022 May;81(5):601-613. doi: 10.1136/annrheumdis-2021-221814. Epub 2022 Jan 27.

Time to Transplant in X-Linked Adrenoleukodystrophy. Bonkowsky JL, Wilkes J. J Child Neurol. 2022 Apr;37(5):397-400. doi: 10.1177/08830738221081141. Epub 2022 Mar 3.

Cerebral X-linked adrenoleukodystrophy (cALD) is a disorder characterized by the destruction of myelin (the insulation surrounding nerve fibers) in the brain. Survival and improved outcomes for cALD are associated with hematopoietic stem cell transplantation (HSCT) at earliest evidence of disease on magnetic resonance imaging (MRI). In this study, researchers aimed to determine average duration between diagnosis of cALD and HSCT. Among 27 patients with cALD in the hospitals they evaluated, the team found that time to HSCT was greater than 3 months. They also noted differences in average time by race/ethnicity and by hospital. Authors state that these findings suggest an opportunity to reduce time to transplant in cALD.

Wearable sensors detect impaired gait and coordination in LBSL during remote assessments. Smith Fine A, Kaufman M, Goodman J, Turk B, Bastian A, Lin D, Fatemi A, Keller J. Ann Clin Transl Neurol. 2022 Apr;9(4):468-477. doi: 10.1002/acn3.51509. Epub 2022 Mar 8.

Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy. Gavazzi F, Charsar BA, Williams C, Shults J, Alves CA, Adang L, Vanderver A. J Child Neurol. 2021 Apr 12:883073821000977. doi: 10.1177/0883073821000977. Online ahead of print.

Adrenal insufficiency updates in children. Ramirez Alcantara J, Halper A. Curr Opin Endocrinol Diabetes Obes. 2021 Feb 1;28(1):75-81. doi: 10.1097/MED.0000000000000591.

Hepatic Involvement in Aicardi-Goutières Syndrome. Gavazzi F, Cross ZM, Woidill S, McMann JM, Rand EB, Takanohashi A, Ulrick N, Shults J, Vanderver AL, Adang L. Neuropediatrics. 2021 Dec;52(6):441-447. doi: 10.1055/s-0040-1722673. Epub 2021 Jan 14.

Interocular Difference in Retinal Nerve Fiber Layer Thickness Predicts Optic Neuritis in Pediatric-Onset Multiple Sclerosis. Waldman AT, Benson L, Sollee JR, Lavery AM, Liu GW, Green AJ, Waubant E, Heidary G, Conger D, Graves J, Greenberg B. J Neuroophthalmol. 2021 Dec 1;41(4):469-475. doi: 10.1097/WNO.0000000000001070.

Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features. Piccoli C, Bronner N, Gavazzi F, Dubbs H, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Masnada S, Tonduti D, Varesio C, Vanderver A, Vossough A, Adang L. Pediatr Neurol. 2021 Feb;115:1-6. doi: 10.1016/j.pediatrneurol.2020.10.012. Epub 2020 Nov 2.

MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines. Mallack EJ, Turk BR, Yan H, Price C, Demetres M, Moser AB, Becker C, Hollandsworth K, Adang L, Vanderver A, Van Haren K, Ruzhnikov M, Kurtzberg J, Maegawa G, Orchard PJ, Lund TC, Raymond GV, Regelmann M, Orsini JJ, Seeger E, Kemp S, Eichler F, Fatemi A. J Inherit Metab Dis. 2021 May;44(3):728-739. doi: 10.1002/jimd.12356. Epub 2021 Jan 9.

National U.S. Patient and Transplant Data for Krabbe Disease. Ghabash G, Wilkes J, Bonkowsky JL. Front Pediatr. 2021 Nov 11;9:764626. doi: 10.3389/fped.2021.764626. eCollection 2021.

Reliability of the Telemedicine Application of the Gross Motor Function Measure-88 in Patients With Leukodystrophy. Gavazzi F, Adang L, Waldman A, Jan AK, Liu G, Lorch SA, DeMauro SB, Shults J, Pierce SR, Ballance E, Kornafel T, Harrington A, Glanzman AM, Vanderver A. Pediatr Neurol. 2021 Dec;125:34-39. doi: 10.1016/j.pediatrneurol.2021.09.012. Epub 2021 Sep 24. PMID: 34624609; PMCID: PMC8629609.

Leukodystrophies are a group of rare neurological disorders affecting the white matter of the brain that are characterized by severe neuromotor disability. Research on the functional status of people with leukodystrophy is limited by the need for in-person mobility assessments. The Gross Motor Function Measure-88 (GMFM-88) is an assessment tool used to measure change in gross motor function over time. In this study, researchers assessed the reliability of the GMFM-88 using telemedicine compared with standard in-person assessments in patients with leukodystrophy. They found that remote application of the GMFM-88 is a feasible and reliable approach. The authors note that this approach may be of particular value in rare diseases and those with severe neurologic disability that impacts travel ability.

Development of a neurologic severity scale for Aicardi Goutières Syndrome. Adang LA, Gavazzi F, Jawad AF, Cusack SV, Kopin K, Peer K, Besnier C, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Shults J, Vanderver A. Mol Genet Metab. 2020 Jun;130(2):153-160. doi: 10.1016/j.ymgme.2020.03.008. Epub 2020 Apr 2.

Janus Kinase Inhibition in the Aicardi-Goutières Syndrome. Vanderver A, Adang L, Gavazzi F, McDonald K, Helman G, Frank DB, Jaffe N, Yum SW, Collins A, Keller SR, Lebon P, Meritet JF, Rhee J, Takanohashi A, Armangue T, Ulrick N, Sherbini O, Koh J, Peer K, Besnier C, Scher C, Boyle K, Dubbs H, Kramer-Golinkoff J, Pizzino A, Woidill S, Shults J. N Engl J Med. 2020 Sep 3;383(10):986-989. doi: 10.1056/NEJMc2001362.

Racial/Ethnic and Insurance Status Disparities in Distance Traveled to Access Children's Hospital Care for Severe Illness: the Case of Children with Leukodystrophies. Grineski SE, Morales DX, Collins T, Wilkes J, Bonkowsky JL. J Racial Ethn Health Disparities. 2020 Oct;7(5):975-986. doi: 10.1007/s40615-020-00722-w. Epub 2020 Feb 24.

Randomized Clinical Trial of First-Line Genome Sequencing in Pediatric White Matter Disorders. Vanderver A, Bernard G, Helman G, Sherbini O, Boeck R, Cohn J, Collins A, Demarest S, Dobbins K, Emrick L, Fraser JL, Masser-Frye D, Hayward J, Karmarkar S, Keller S, Mirrop S, Mitchell W, Pathak S, Sherr E, van Haren K, Waters E, Wilson JL, Zhorne L, Schiffmann R, van der Knaap MS, Pizzino A, Dubbs H, Shults J, Simons C, Taft RJ; LeukoSEQ Workgroup. Ann Neurol. 2020 Aug;88(2):264-273. doi: 10.1002/ana.25757. Epub 2020 Jun 9.

Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. Hum Mutat. 2020 Jun;41(6):1131-1137. doi: 10.1002/humu.24008. Epub 2020 Mar 11.

Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A. Tomaselli PJ, Blake J, Polke JM, do Nascimento OJM, Reilly MM, Marques Júnior W, Laurá M. Eur J Neurol. 2024 Feb 26:e16199. doi: 10.1111/ene.16199. Epub ahead of print. PMID: 38409938.

Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of inherited peripheral neuropathy, is caused by duplication of the PMP22 gene. Individuals with CMT1A experience slow nerve conduction velocity (the speed of electrical impulses moving through nerves). Because most patients have nerve conduction rates below 38 meters per second, genetic testing for PMP22 duplication is not usually recommended for those with higher rates. 

In this study, researchers report cases of intermediate nerve conduction velocity in two patients with CMT1A. Both individuals had upper limb motor nerve conduction velocities above 38 meters per second. These patients also presented with very mild forms of CMT1A.

Authors note that although these cases are very rare, they highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

Advances in diagnosis and management of distal sensory polyneuropathies. Silsby M, Feldman EL, Dortch RD, Roth A, Haroutounian S, Rajabally YA, Vucic S, Shy ME, Oaklander AL, Simon NG. J Neurol Neurosurg Psychiatry. 2023 Mar 30:jnnp-2021-328489. doi: 10.1136/jnnp-2021-328489. Online ahead of print.

Association of Body Mass Index With Disease Progression in Children With Charcot-Marie-Tooth Disease. Donlevy GA, Cornett KMD, Garnett SP, Shy R, Estilow T, Yum SW, Anderson K, Pareyson D, Moroni I, Muntoni F, Reilly MM, Finkel RS, Herrmann DN, Eichinger KJ, Shy ME, Burns J, Menezes MP. Neurology. 2023 Aug 15;101(7):e717-e727. doi: 10.1212/WNL.0000000000207488. Epub 2023 Jun 28. PMID: 37380432; PMCID: PMC10437011

Charcot-Marie-Tooth disease (CMT) is a group of disorders that affect the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells. Symptoms include weakness, sensory loss, muscle atrophy (wasting), and foot deformities.

In this study, researchers evaluated the impact of body mass index (BMI) on disease progression over two years in children with CMT. Among 242 participants aged 3–20 years with CMT, the team categorized groups by BMI and assessed disease severity using the CMT Pediatric Scale (CMTPedS).

Results show that children with CMT who were severely underweight, underweight, or obese exhibited greater disability at baseline. Over the two-year period in those whose BMI remained stable, severely underweight children deteriorated at the fastest rate. For children who changed BMI categories over the two years, CMTPedS scores deteriorated faster in those who became overweight or obese. Authors note that interventions to maintain or improve BMI toward healthy weight may reduce disability in children with CMT.

Beware next-generation sequencing gene panels as the first-line genetic test in Charcot-Marie-Tooth disease. Record CJ, Pipis M, Poh R, Polke JM, Reilly MM. J Neurol Neurosurg Psychiatry. 2023 Apr;94(4):327-328. doi: 10.1136/jnnp-2022-330223. Epub 2022 Nov 14.

Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs. Rebelo AP, Tomaselli PJ, Medina J, Wang Y, Dohrn MF, Nyvltova E, Danzi MC, Garrett M, Smith SE, Pestronk A, Li C, Ruiz A, Jacobs E, Feely SME, França MC, Gomes MV, Santos DF, Kumar S, Lombard DB, Saporta M, Hekimi S, Barrientos A, Weihl C, Shy ME, Marques W, Zuchner S. Brain. 2023 Oct 3;146(10):4191-4199. doi: 10.1093/brain/awad158.

Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations: A Longitudinal Study. Fridman V, Sillau S, Bockhorst J, Smith K, Moroni I, Pagliano E, Pisciotta C, Piscosquito G, Laurá M, Muntoni F, Bacon C, Feely S, Grider T, Gutmann L, Shy R, Wilcox J, Herrmann DN, Li J, Ramchandren S, Sumner CJ, Lloyd TE, Day J, Siskind CE, Yum SW, Sadjadi R, Finkel RS, Scherer SS, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium-Rare Diseases Clinical Research Network. Ann Neurol. 2023 Mar;93(3):563-576. doi: 10.1002/ana.26518. Epub 2022 Oct 28.

Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants. Record CJ, Skorupinska M, Laura M, Rossor AM, Pareyson D, Pisciotta C, Feely SME, Lloyd TE, Horvath R, Sadjadi R, Herrmann DN, Li J, Walk D, Yum SW, Lewis RA, Day J, Burns J, Finkel RS, Saporta MA, Ramchandren S, Weiss MD, Acsadi G, Fridman V, Muntoni F, Poh R, Polke JM, Zuchner S, Shy ME, Scherer SS, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network. Brain. 2023 Jun 7:awad187. doi: 10.1093/brain/awad187. Online ahead of print.

Mutations in alpha-B-crystallin cause autosomal dominant axonal Charcot-Marie-Tooth disease with congenital cataracts. Cortese A, Currò R, Ronco R, Blake J, Rossor AM, Bugiardini E, Laurà M, Warner T, Yousry T, Poh R, Polke J, Rebelo A, Dohrn MF, Saporta M, Houlden H, Zuchner S, Reilly MM. Eur J Neurol. 2023 Sep 29. doi: 10.1111/ene.16063. Epub ahead of print. PMID: 37772343

Charcot–Marie–Tooth disease type 2 (CMT2), also known as hereditary motor and sensory neuropathy, is a disorder affecting nerve axons (ends of the nerves) which carry signals from the brain to the extremities. While mutations in the alpha-B-crystallin (CRYAB) gene have been associated with myofibrillar myopathy, dilated cardiomyopathy, and cataracts, they have not previously included peripheral neuropathy.

In this study, researchers expand the phenotype (observable characteristics) of CRYAB-related disease to include CMT2. The team performed whole-exome sequencing in two unrelated families with genetically unsolved axonal CMT2, assessing clinical, neurophysiological, and radiological features.

Results identify CRYAB mutations as a cause of CMT2 in these patients. Authors note that CRYAB mutations should be suspected in cases with late-onset CMT2, especially in the presence of congenital cataracts.

Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history. Rehbein T, Wu TT, Treidler S, Pareyson D, Lewis R, Yum SW, McCray BA, Ramchandren S, Burns J, Li J, Finkel RS, Scherer SS, Zuchner S, Shy ME, Reilly MM, Herrmann DN. Brain. 2023 Sep 1;146(9):3826-3835. doi: 10.1093/brain/awad095. PMID: 36947133; PMCID: PMC10473553

Charcot-Marie-Tooth disease type 4C (CMT4C) is an inherited, degenerative disorder affecting the nerves that travel to the feet and hands. CMT4C is caused by recessive variants in the SH3TC2 gene and characterized by early onset spinal deformities, as well as a wide spectrum of symptoms and severity. Currently, not much is known about the relationship between pathogenic (disease-causing) variants and disease manifestations.

In this study, researchers explored the natural history of CMT4C by gathering genetic and clinical data from the Inherited Neuropathy Consortium (INC). The team examined symptoms, neurological examinations, and neurophysiological characteristics over time in 56 individuals with CMT4C.

The resulting analysis marks the largest cross-sectional and only longitudinal study to date of the clinical phenotype of both adults and children with CMT4C. Authors note that by further defining the natural history of CMT4C, these data will help inform study design of future clinical trials for genetic treatments.

Post-transcriptional microRNA repression of PMP22 dose in severe Charcot-Marie-Tooth disease type 1. Pipis M, Won S, Poh R, Efthymiou S, Polke JM, Skorupinska M, Blake J, Rossor AM, Moran JJ, Munot P, Muntoni F, Laura M, Svaren J, Reilly MM. Brain. 2023 Oct 3;146(10):4025-4032. doi: 10.1093/brain/awad203. PMID: 37337674; PMCID: PMC10545524

Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of inherited peripheral neuropathy, is caused by a copy number variation (CNV) in the PMP22 gene. In rodent models of CMT1A, overexpression of miR-29a, a type of microRNA, has been shown to reduce the PMP22 transcript and protein level.

In this study, researchers demonstrate for the first time how imbalance in the microRNA-mediated regulation of gene expression can mimic a CNV-associated disease in humans. Study participants included a family of CMT1A patients enrolled in a natural history study.

Authors state that these findings show the importance of miR-29a in regulating PMP22 expression and could lead to development of new therapeutic drugs.

Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency. Zhu Y, Lobato AG, Rebelo AP, Canic T, Ortiz-Vega N, Tao X, Syed S, Yanick C, Saporta M, Shy M, Perfetti R, Shendelman S, Züchner S, Zhai RG. JCI Insight. 2023 May 22;8(10):e164954. doi: 10.1172/jci.insight.164954.

Thirty-Year Follow-Up of Early Onset Amyotrophic Lateral Sclerosis with a Pathogenic Variant in SPTLC1. Ajjarapu A, Feely SME, Shy ME, Trout C, Zuchner S, Moore SA, Mathews KD. Case Rep Neurol. 2023 Jun 12;15(1):146-152. doi: 10.1159/000530974. eCollection 2023 Jan-Dec.

Trials for Slowly Progressive Neurogenetic Diseases Need Surrogate Endpoints. Reilly MM, Herrmann DN, Pareyson D, Scherer SS, Finkel RS, Züchner S, Burns J, Shy ME. Ann Neurol. 2023 May;93(5):906-910. doi: 10.1002/ana.26633. Epub 2023 Mar 21.

Validation of the parent-proxy pediatric Charcot-Marie-Tooth disease quality of life outcome measure. Wu TT, Finkel RS, Siskind CE, Feely SME, Burns J, Reilly MM, Muntoni F, Estilow T, Shy ME, Ramchandren S; Childhood CMT Study Group of the Inherited Neuropathy Consortium. J Peripher Nerv Syst. 2023 Feb 7. doi: 10.1111/jns.12538. Epub ahead of print. PMID: 36748295.

Charcot-Marie-Tooth disease (CMT) is a group of genetic disorders that affect the peripheral nerves, which connect the brain and spinal cord to muscles and sensory endings. With symptoms including weakness, sensory loss, muscle atrophy (wasting), balance problems, and foot deformities, CMT is known to reduce health-related quality of life (QOL) in children as well as adults. However, there is currently no parent-proxy CMT QOL outcome measure for use in children for either natural history studies or clinical trials. 

In this study, researchers describe the validation of the parent-proxy pediatric CMT-QOL outcome measure for children aged 8 to 18 years. After developing a working version of the outcome measure, the team administered this version to 358 parents of children with CMT seen at the participating study sites of the Inherited Neuropathy Consortium from 2010 to 2016. Results from the parent-proxy version were compared with previously published results completed by the children themselves. To develop the final version, researchers performed rigorous tests of the data, including psychometric analysis, factor analysis, test-retest reliability, internal consistency, convergent validity, IRT analysis, and longitudinal analysis.

Results show that the parent-proxy version of the pediatric CMT-QOL outcome measure is a reliable, valid, and sensitive proxy measure of health-related QOL for children aged 8 to 18 with CMT.

Validation of the parent-proxy version of the pediatric Charcot-Marie-Tooth disease quality of life instrument for children aged 0-7 years. Wu TT, Finkel RS, Siskind CE, Feely SME, Burns J, Reilly MM, Muntoni F, Milev E, Estilow T, Shy ME, Ramchandren S; Childhood CMT Study Group of the Inherited Neuropathy Consortium. J Peripher Nerv Syst. 2023 Sep;28(3):382-389. doi: 10.1111/jns.12557. Epub 2023 May 18.

A neuropathy-associated kinesin KIF1A mutation hyper-stabilizes the motor-neck interaction during the ATPase cycle. Morikawa M, Jerath NU, Ogawa T, Morikawa M, Tanaka Y, Shy ME, Zuchner S, Hirokawa N. EMBO J. 2022 Mar 1;41(5):e108899. doi: 10.15252/embj.2021108899. Epub 2022 Feb 8. PMID: 35132656.

Charcot-Marie-Tooth (CMT) is a group of inherited, degenerative disorders affecting the nerves that travel to the feet and hands, causing muscle weakness, problems with balance and sensation as well as other symptoms. Axonal transport (a process essential for nerve development, function, and survival) mediated by the KIF1A gene is driven by interaction cycles between the kinesin (motor protein)’s motor and neck domains. In this study, researchers characterized a KIF1A mutant identified in a family with axonal-type CMT and other cases of human neuropathies. This characterization reveals that dynamic dissociation of the motor-neck interaction via the β7 (integrin protein) domain is essential for neuronal function.

Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A. Eichinger K, Sowden JE, Burns J, McDermott MP, Krischer J, Thornton J, Pareyson D, Scherer SS, Shy ME, Reilly MM, Herrmann DN. Front Neurol. 2022 Jun 27;13:930435. doi: 10.3389/fneur.2022.930435. eCollection 2022.

Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy. Kapoor M, Carr A, Foiani M, Heslegrave A, Zetterberg H, Malaspina A, Compton L, Hutton E, Rossor A, Reilly MM, Lunn MP. Eur J Neurol. 2022 Nov;29(11):3347-3357. doi: 10.1111/ene.15496. Epub 2022 Jul 25.

Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype. Pipis M, Cortese A, Polke JM, Poh R, Vandrovcova J, Laura M, Skorupinska M, Jacquier A, Juntas-Morales R, Latour P, Petiot P, Sole G, Fromes Y, Shah S, Blake J, Choi BO, Chung KW, Stojkovic T, Rossor AM, Reilly MM. J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):48-56. doi: 10.1136/jnnp-2021-327186. Epub 2021 Sep 13. PMID: 34518334; PMCID: PMC8685631.

Researchers seeking to better understand axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC) conducted an observational study of 30 affected and 3 asymptomatic mutation carriers from 8 families, examining phenotype-genotype correlations. Study subjects had variants in the gene NEFH, which is thought to cause CMT2CC. Researchers found that most patients developed lower-limb predominant symptoms in adulthood. The disease progressed more rapidly than is typically seen in other CMT subtypes, and half of patients needed to use a wheelchair an average of 24.1 years after symptoms began. They found that that the unusual phenotype of CMT2CC is more similar to spinal muscular atrophy than classic CMT. Study authors said that these findings should allow a better understanding of the natural history of the disease and aid in variant interpretation.

Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease. Yiu EM, Bray P, Baets J, Baker SK, Barisic N, de Valle K, Estilow T, Farrar MA, Finkel RS, Haberlová J, Kennedy RA, Moroni I, Nicholson GA, Ramchandren S, Reilly MM, Rose K, Shy ME, Siskind CE, Yum SW, Menezes MP, Ryan MM, Burns J. J Neurol Neurosurg Psychiatry. 2022 May;93(5):530-538. doi: 10.1136/jnnp-2021-328483. Epub 2022 Feb 9.

HINT1 neuropathy in Lithuania: clinical, genetic, and functional profiling. Malcorps M, Amor-Barris S, Burnyte B, Vilimiene R, Armirola-Ricaurte C, Grigalioniene K, Ekshteyn A, Morkuniene A, Vaitkevicius A, De Vriendt E, Baets J, Scherer SS, Ambrozaityte L, Utkus A, Jordanova A, Peeters K. Orphanet J Rare Dis. 2022 Oct 14;17(1):374. doi: 10.1186/s13023-022-02541-0. PMID: 36242072; PMCID: PMC9569031.

Neuromyotonia and axonal neuropathy (NMAN) is a rare peripheral neuropathy and subtype of Charcot-Marie-Tooth disease. NMAN is characterized by damage to nerve axons (nerve ends) and overactivation of peripheral nerves. The disease is caused by mutations in the HINT1 gene, which are among the most common causes of recessive neuropathy. Most patients with NMAN are found to have an HINT1 variant that has spread throughout Eurasia and America. In this study, researchers performed the first analysis of NMAN in Lithuania. The team identified eight patients from 46 families with variations in the HINT1 gene, including a new variant. Study participants showed typical symptoms associated with NMAN (such as motor impairment in lower limbs), but also some atypical features (such as developmental delay and mood problems). In addition to expanding the understanding of NMAN, these findings may help diagnose inherited neuropathies in the Baltic region and beyond. Authors note that study results could also impact future therapeutic strategies, as a patient’s specific genetic mutation will determine their treatment options.

Severe distinct dysautonomia in RFC1-related disease associated with Parkinsonism. Record CJ, Alsukhni RA, Curro R, Kaski D, Rubin JS, Morris HR, Cortese A, Iodice V, Reilly MM. J Peripher Nerv Syst. 2022 Sep 30. doi: 10.1111/jns.12515. Epub ahead of print. PMID: 36177974.

Recently, biallelic (both alleles of a single gene) expansions in the RFC1 gene have been found to cause several neurological disorders in addition to a form of inherited neuropathy known as CANVAS (cerebellar ataxia, neuropathy, and vestibular areflexia syndrome). There are also descriptions of Parkinsonism and a multiple system atrophy (MSA)-like syndrome. However, the profile of the autonomic nervous system in a patient with CANVAS/MSA-like overlap syndrome had not yet been fully characterized. In this study, researchers present the first detailed description of autonomic characteristics in a patient with multisystem RFC1-related disease. Initially presenting with CANVAS, the patient developed Parkinsonism, cardiovascular failure, and severe autonomic failure similar to classical MSA. Results suggest that patients with an MSA-like syndrome, plus signs of vestibular (balance) failure or sensory neuropathy, should be tested for the RFC1 expansion. Authors also note that the link between MSA and CANVAS should be further explored.

Unusual upper limb features in SORD neuropathy. Record CJ, Pipis M, Blake J, Curro R, Lunn MP, Rossor AM, Laura M, Cortese A, Reilly MM. J Peripher Nerv Syst. 2022 Apr 13. doi: 10.1111/jns.12492. Online ahead of print.

A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement. Rebelo AP, Cortese A, Abraham A, Eshed-Eisenbach Y, Shner G, Vainshtein A, Buglo E, Camarena V, Gaidosh G, Shiekhattar R, Abreu L, Courel S, Burns DK, Bai Y, Bacon C, Feely SME, Castro D, Peles E, Reilly MM, Shy ME, Zuchner S. Brain. 2021 May 7;144(4):1197-1213. doi: 10.1093/brain/awab019.

Researchers used whole exome sequencing in three unrelated families with axonal Charcot-Marie-Tooth disease (CMT2) to identify a unique pathogenic variant causing CMT with marked upper limb involvement. CMT2 is a group of genetic neuropathies that primarily cause axonal degeneration (damage to the portion of the nerve that carries nerve impulses away from the cell body). The variant identified is in the CADM family of proteins, which mediate the contact and interaction between axons and the glia (non-neuronal cells that form myelin in the peripheral nervous system and support and protect neurons). The families studied all shared the same private variant in CADM3, Tyr172Cys. Findings were also confirmed in mouse studies. Researchers conclude that this abnormal axon-glia interaction is a disease-causing mechanism in CMT patients with CADM3 mutations. This is the first example that directly disrupting the interactions between glia and axons is sufficient to cause neuropathy.

A longitudinal and cross-sectional study of plasma neurofilament light chain concentration in Charcot-Marie-Tooth disease. Rossor AM, Kapoor M, Wellington H, Spaulding E, Sleigh JN, Burgess RW, Laura M, Zetterberg H, Bacha A, Wu X, Heslegrave A, Shy ME, Reilly MM. J Peripher Nerv Syst. 2021 Dec 1. doi: 10.1111/jns.12477. Online ahead of print.

A novel MT-CO2 variant causing cerebellar ataxia and neuropathy: The role of muscle biopsy in diagnosis and defining pathogenicity. Baty K, Farrugia ME, Hopton S, Falkous G, Schaefer AM, Stewart W, Willison HJ, Reilly MM, Blakely EL, Taylor RW, Ng YS. Neuromuscul Disord. 2021 Nov;31(11):1186-1193. doi: 10.1016/j.nmd.2021.05.014. Epub 2021 Jun 4.

A prospective study on surgical management of foot deformities in Charcot Marie tooth disease. Ramdharry G, Singh D, Gray J, Kozyra D, Skorupinska M, Reilly MM, Laurá M. J Peripher Nerv Syst. 2021 Jun;26(2):187-192. doi: 10.1111/jns.12437. Epub 2021 Mar 13.

A recurrent MORC2 mutation causes Charcot-Marie-Tooth disease type 2Z. Vujovic D, Cornblath DR, Scherer SS. J Peripher Nerv Syst. 2021 Apr 12. doi: 10.1111/jns.12443. Online ahead of print.

An approach to assessing immunoglobulin dependence in chronic inflammatory demyelinating inflammatory polyneuropathy. Kapoor M, Compton L, Rossor A, Hutton E, Manji H, Lunn M, Reilly M, Carr A. J Peripher Nerv Syst. 2021 Dec;26(4):461-468. doi: 10.1111/jns.12470. Epub 2021 Oct 20.

An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions. Clark AJ, Kugathasan U, Baskozos G, Priestman DA, Fugger N, Lone MA, Othman A, Chu KH, Blesneac I, Wilson ER, Laurà M, Kalmar B, Greensmith L, Hornemann T, Platt FM, Reilly MM, Bennett DL. Cell Rep Med. 2021 Jul 21;2(7):100345. doi: 10.1016/j.xcrm.2021.100345. eCollection 2021 Jul 20.

Axonal Charcot-Marie-Tooth Disease: from Common Pathogenic Mechanisms to Emerging Treatment Opportunities. McCray BA, Scherer SS. Neurotherapeutics. 2021 Oct 4. doi: 10.1007/s13311-021-01099-2. Online ahead of print.

In this review paper, two researchers associated with the Inherited Neuropathies Consortium offer an overview of Charcot-Marie-Tooth disease type 2 (CMT2), a group of genetic neuropathies that primarily cause axonal degeneration (damage to the portion of the nerve that carries nerve impulses away from the cell body) rather than demyelination (damage to the protective covering that surrounds nerve fibers). They review gene identification efforts over the past three decades and emerging treatment strategies. Promising strategies include specific approaches for single forms of neuropathy as well as more general approaches that have the potential to treat multiple types of neuropathy. The INC is particularly pleased because coauthor Brett Andrew McCray, MD, PhD of Johns Hopkins is a recent INC scholar who was supported by a Career Enhancement Award.

Cardiopulmonary exercise performance and factors associated with aerobic capacity in neuromuscular diseases. Ramdharry GM, Wallace A, Hennis P, Dewar E, Dudziec M, Jones K, Pietrusz A, Reilly MM, Hanna MG. Muscle Nerve. 2021 Dec;64(6):683-690. doi: 10.1002/mus.27423. Epub 2021 Oct 6.

Development and Validation of the Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure. Ramchandren S, Wu TT, Finkel RS, Siskind CE, Feely SME, Burns J, Reilly MM, Estilow T, Shy ME; Childhood CMT Study Group. Ann Neurol. 2021 Feb;89(2):369-379. doi: 10.1002/ana.25966. Epub 2020 Dec 7.

Enrichment of SARM1 alleles encoding variants with constitutively hyperactive NADase in patients with ALS and other motor nerve disorders. Gilley J, Jackson O, Pipis M, Estiar MA, Al-Chalabi A, Danzi MC, van Eijk KR, Goutman SA, Harms MB, Houlden H, Iacoangeli A, Kaye J, Lima L; Queen Square Genomics, Ravits J, Rouleau GA, Schüle R, Xu J, Züchner S, Cooper-Knock J, Gan-Or Z, Reilly MM, Coleman MP. Elife. 2021 Nov 19;10:e70905. doi: 10.7554/eLife.70905. PMID: 34796871; PMCID: PMC8735862.

SARM1 is a protein with critical NAD-glycohydrolase (NADase) activity. This protein drives axon (nerve fiber) degeneration, a characteristic of many neurodegenerative diseases. In this study, researchers screened patient data for mutations associated with amyotrophic lateral sclerosis (ALS). They discovered disease-associated variant alleles that alter SARM1 function, hyperactivating the NADase activity that drives degeneration. The authors conclude that these may represent risk alleles for ALS and other motor nerve diseases. These findings highlight the role of axonal degeneration in motor neuron diseases. The study also provides a rationale for SARM1-directed therapeutic intervention.

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature. Jurkute N, Shanmugarajah PD, Hadjivassiliou M, Higgs J, Vojcic M, Horrocks I, Nadjar Y, Touitou V, Lenaers G, Poh R, Acheson J, Robson AG, Raymond FL, Reilly MM, Yu-Wai-Man P, Moore AT, Webster AR, Arno G; Genomics England Research Consortium. Invest Ophthalmol Vis Sci. 2021 May 3;62(6):2. doi: 10.1167/iovs.62.6.2.

Loss of function MPZ mutation causes milder CMT1B neuropathy. Howard P, Feely SME, Grider T, Bacha A, Scarlato M, Fazio R, Quattrini A, Shy ME, Previtali SC. J Peripher Nerv Syst. 2021 May 7. doi: 10.1111/jns.12452. Online ahead of print.

MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A. Wang H, Davison M, Wang K, Xia TH, Call KM, Luo J, Wu X, Zuccarino R, Bacha A, Bai Y, Gutmann L, Feely SME, Grider T, Rossor AM, Reilly MM, Shy ME, Svaren J. Neurology. 2021 Aug 3;97(5):e489-e500. doi: 10.1212/WNL.0000000000012266. Epub 2021 May 24.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited neurological disorder that affects the peripheral nerves of patients, causing weakness and wasting of the muscles of the lower legs, hand weakness, and sensory loss. To identify candidate biomarkers for clinical trials in CMT1A, researchers performed microRNA (miR) profiling on control and CMT1A plasma with the goal of determining whether microRNAs are elevated in affected individuals. Results confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerves. Authors say the study provides Class III evidence that a set of plasma mIRs are elevated in patients with CMT1A.

Optic Neuropathy in Charcot-Marie-Tooth Disease. Hamedani AG, Wilson JA, Avery RA, Scherer SS. J Neuro Ophthalmol. 2021 Jun 1;41(2):233-238. doi: 10.1097/WNO.0000000000000965.

RFC1-related ataxia is a mimic of early multiple system atrophy. Sullivan R, Yau WY, Chelban V, Rossi S, Dominik N, O'Connor E, Hardy J, Wood N, Cortese A, Houlden H. J Neurol Neurosurg Psychiatry. 2021 Feb 9;92(4):444-6. doi: 10.1136/jnnp-2020-325092. Online ahead of print.

Rare mutations in ATL3, SPTLC2 and SCN9A explaining hereditary sensory neuropathy and congenital insensitivity to pain in a Brazilian cohort. Cintra VP, Dohrn MF, Tomaselli PJ, Figueiredo FB, Marques SE, Camargos ST, Barbosa LSM, P Rebelo A, Abreu L, Danzi M, Marques W Jr, Züchner S. J Neurol Sci. 2021 Aug 15;427:117498. doi: 10.1016/j.jns.2021.117498. Epub 2021 May 18.

Heredity sensory neuropathies (HSNs) are rare neurological disorders where peripheral neurons and axons are affected, leading to delayed sensations of pain, delayed healing, infections, osteomyelitis, and infections. Researchers performed a whole genome sequencing (WGS) study of 23 unrelated Brazilian families diagnosed with hereditary sensory neuropathies. They detected pathogenic variants in 21.7% of families that caused symptoms such as congenital insensitivity to pain, sensory deficits, neuropathic pain, and recurrent ulcerations. Authors suggest that most of the cases could be explained by yet to be discovered genes or unusual alleles. They say that first mutational screen in a Brazilian HSN cohort offers insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.

Satisfaction with ankle foot orthoses in individuals with Charcot-Marie-Tooth disease. Zuccarino R, Anderson KM, Shy ME, Wilken JM. Muscle Nerve. 2021 Jan;63(1):40-45. doi: 10.1002/mus.27027. Epub 2020 Aug 26.

The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy. Spaulding EL, Hines TJ, Bais P, Tadenev ALD, Schneider R, Jewett D, Pattavina B, Pratt SL, Morelli KH, Stum MG, Hill DP, Gobet C, Pipis M, Reilly MM, Jennings MJ, Horvath R, Bai Y, Shy ME, Alvarez-Castelao B, Schuman EM, Bogdanik LP, Storkebaum E, Burgess RW. Science. 2021 Sep 3;373(6559):1156-1161. doi: 10.1126/science.abb3414. Epub 2021 Sep 1.

Researchers have identified a pathway common to several types of axonal peripheral neuropathies (APNs), including multiple forms of Charcot-Marie-Tooth (CMT) disease, and have identified a possible drug target that could help treat the disorder. The research was led by Robert W. Burgess, PhD, Emily Spaulding, and their team at The Jackson Laboratory in Maine. Researchers with the RDCRN’s Inherited Neuropathies Consortium (INC) contributed by providing patient material to add a human disease component to the team’s efforts. “The serum samples provide by the INC were a way for us to test whether the same mechanisms we found in our mouse models were also involved in patients,” says Burgess, senior author on the study. “As an unexpected bonus, it led to the identification of GDF15 as a possible biomarker, which is being investigated further.” The study, which was published in Science, was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and featured in a recent NIH media advisory. APNs cause the body’s peripheral nerves to wither and degenerate, which makes them unable to send messages to the muscles or to transmit sensory signals back to the spinal cord. While usually not life-threatening, APNs typically result in some measure of disability. Genetic studies have shown that many APNs are caused by mutations that affect how proteins are built within cells. Proteins are made by first transcribing the DNA code into messenger RNA (mRNA). The mRNA is then transcribed by transfer RNA (tRNA) molecules that string together amino acids in the proper sequence, like building a train track. The mutations underlying APNs affect the enzymes responsible for adding amino acid blocks to tRNA. Previous work in flies showed that these mutations inhibit cells’ ability to make proteins. This causes stress within the motor neurons affected by APNs, particularly through a mechanism called the integrated stress response (ISR), ultimately leading to degeneration of nerve structures. Of the proteins previously implicated in the activation of the ISR, one of them, GCN2, had also been connected to defects in protein translation. Using a mouse model, the researchers looked at APN mice that were also missing GCN2. These mice began to develop symptoms of the disease around two weeks of age, but the disease did not progress much beyond the initial stages. When the APN mice were instead treated with a drug to stop GCN2 from working, they showed improvements in many symptoms.

A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. Beecroft SJ, Cortese A, Sullivan R, Yau WY, Dyer Z, Wu TY, Mulroy E, Pelosi L, Rodrigues M, Taylor R, Mossman S, Leadbetter R, Cleland J, Anderson T, Ravenscroft G, Laing NG, Houlden H, Reilly MM, Roxburgh RH. Brain. 2020 Sep 1;143(9):2673-2680. doi: 10.1093/brain/awaa203.

A dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease. Edgar JR, Ho AK, Laurá M, Horvath R, Reilly MM, Luzio JP, Roberts RC. Acta Neuropathol Commun. 2020 Oct 15;8(1):165. doi: 10.1186/s40478-020-01043-z.

A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores. Fridman V, Sillau S, Acsadi G, Bacon C, Dooley K, Burns J, Day J, Feely S, Finkel RS, Grider T, Gutmann L, Herrmann DN, Kirk CA, Knause SA, Laurá M, Lewis RA, Li J, Lloyd TE, Moroni I, Muntoni F, Pagliano E, Pisciotta C, Piscosquito G, Ramchandren S, Saporta M, Sadjadi R, Shy RR, Siskind CE, Sumner CJ, Walk D, Wilcox J, Yum SW, Züchner S, Scherer SS, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium—Rare Diseases Clinical Research Network (INC-RDCRN). Neurology. 2020 Mar 3;94(9):e884-e896. doi: 10.1212/WNL.0000000000009035. Epub 2020 Feb 11.

A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. Scriba CK, Beecroft SJ, Clayton JS, Cortese A, Sullivan R, Yau WY, Dominik N, Rodrigues M, Walker E, Dyer Z, Wu TY, Davis MR, Chandler DC, Weisburd B, Houlden H, Reilly MM, Laing NG, Lamont PJ, Roxburgh RH, Ravenscroft G. Brain. 2020 Oct 1;143(10):2904-2910. doi: 10.1093/brain/awaa263.

Are we prepared for clinical trials in Charcot-Marie-Tooth disease?. Rossor AM, Shy ME, Reilly MM. Brain Res. 2020 Feb 15;1729:146625. doi: 10.1016/j.brainres.2019.146625. Epub 2019 Dec 30.

Assessing non-Mendelian inheritance in inherited axonopathies. Bis-Brewer DM, Gan-Or Z, Sleiman P; Inherited Neuropathy Consortium, Hakonarson H, Fazal S, Courel S, Cintra V, Tao F, Estiar MA, Tarnopolsky M, Boycott KM, Yoon G, Suchowersky O, Dupré N, Cheng A, Lloyd TE, Rouleau G, Schüle R, Züchner S. Genet Med. 2020 Dec;22(12):2114-2119. doi: 10.1038/s41436-020-0924-0. Epub 2020 Aug 3.

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S, Courel S, Abreu L, Bacon CJ, Bai Y, Bis-Brewer DM, Bugiardini E, Buglo E, Danzi MC, Feely SME, Athanasiou-Fragkouli A, Haridy NA; Inherited Neuropathy Consortium, Isasi R, Khan A, Laurà M, Magri S, Pipis M, Pisciotta C, Powell E, Rossor AM, Saveri P, Sowden JE, Tozza S, Vandrovcova J, Dallman J, Grignani E, Marchioni E, Scherer SS, Tang B, Lin Z, Al-Ajmi A, Schüle R, Synofzik M, Maisonobe T, Stojkovic T, Auer-Grumbach M, Abdelhamed MA, Hamed SA, Zhang R, Manganelli F, Santoro L, Taroni F, Pareyson D, Houlden H, Herrmann DN, Reilly MM, Shy ME, Zhai RG, Zuchner S. Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.

Burst mitofusin activation reverses neuromuscular dysfunction in murine CMT2A. Franco A, Dang X, Walton EK, Ho JN, Zablocka B, Ly C, Miller TM, Baloh RH, Shy ME, Yoo AS, Dorn GW 2nd. Elife. 2020 Oct 19;9:e61119. doi: 10.7554/eLife.61119.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Cortese A, Tozza S, Yau WY, Rossi S, Beecroft SJ, Jaunmuktane Z, Dyer Z, Ravenscroft G, Lamont PJ, Mossman S, Chancellor A, Maisonobe T, Pereon Y, Cauquil C, Colnaghi S, Mallucci G, Curro R, Tomaselli PJ, Thomas-Black G, Sullivan R, Efthymiou S, Rossor AM, Laurá M, Pipis M, Horga A, Polke J, Kaski D, Horvath R, Chinnery PF, Marques W, Tassorelli C, Devigili G, Leonardis L, Wood NW, Bronstein A, Giunti P, Züchner S, Stojkovic T, Laing N, Roxburgh RH, Houlden H, Reilly MM. Brain. 2020 Feb 1;143(2):480-490. doi: 10.1093/brain/awz418.

Charcot-Marie-Tooth Type 2B: A New Phenotype Associated with a Novel RAB7A Mutation and Inhibited EGFR Degradation. Saveri P, De Luca M, Nisi V, Pisciotta C, Romano R, Piscosquito G, Reilly MM, Polke JM, Cavallaro T, Fabrizi GM, Fossa P, Cichero E, Lombardi R, Lauria G, Magri S, Taroni F, Pareyson D, Bucci C. Cells. 2020 Apr 21;9(4):1028. doi: 10.3390/cells9041028.

Genetic modifiers and non-Mendelian aspects of CMT. Bis-Brewer DM, Fazal S, Züchner S. Brain Res. 2020 Jan 1;1726:146459. doi: 10.1016/j.brainres.2019.146459. Epub 2019 Sep 13.

Humans: the ultimate animal models. Reilly MM, Rossor AM. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1132-1136. doi: 10.1136/jnnp-2020-323016. Epub 2020 Aug 7.

Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2. Deng S, Feely SME, Shi Y, Zhai H, Zhan L, Siddique T, Deng HX, Shy ME. Neuromolecular Med. 2020 Mar;22(1):68-72. doi: 10.1007/s12017-019-08564-4. Epub 2019 Aug 29.

Mutation in RNF170 causes sensory ataxic neuropathy with vestibular areflexia: a CANVAS mimic. Cortese A, Callegari I, Currò R, Vegezzi E, Colnaghi S, Versino M, Alfonsi E, Cosentino G, Valente E, Gana S, Tassorelli C, Pichiecchio A, Rossor AM, Bugiardini E, Biroli A, Di Capua D, Houlden H, Reilly MM. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1237-1238. doi: 10.1136/jnnp-2020-323719. Epub 2020 Sep 17.

Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN). Brain. 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323.

Prot2HG: a database of protein domains mapped to the human genome. Stanek D, Bis-Brewer DM, Saghira C, Danzi MC, Seeman P, Lassuthova P, Zuchner S. Database (Oxford). 2020 Jan 1;2020:baz161. doi: 10.1093/database/baz161.

RFC1 Intronic Repeat Expansions Absent in Pathologically Confirmed Multiple Systems Atrophy. Sullivan R, Yau WY, Chelban V, Rossi S, O'Connor E, Wood NW, Cortese A, Houlden H. Mov Disord. 2020 Jul;35(7):1277-1279. doi: 10.1002/mds.28074. Epub 2020 Apr 24.

Reliability of the Charcot-Marie-Tooth functional outcome measure. Bray P, Cornett KMD, Estilow T, Pareyson D, Zuccarino R, Skorupinska M, Pipis M, Sowden JE, Scherer S, Reilly MM, Shy ME, Herrmann DN, Burns J, Eichinger KJ. J Peripher Nerv Syst. 2020 Sep;25(3):288-291. doi: 10.1111/jns.12406. Epub 2020 Aug 26.

Charcot-Marie-Tooth (CMT) is a group of inherited, degenerative disorders affecting the nerves that travel to the feet and hands, causing pain, muscle weakness, and other symptoms. In order to assess disease severity and changes over time, researchers have developed a functional outcome measure called the CMT-FOM. This 13-item clinical outcome assessment tool measures physical ability in adults with Charcot-Marie-Tooth (CMT) disease. To assess inter-rater reliability of the tool, or the degree to which independent observers using the CMT-FOM agree, researchers trained six evaluators in its use. The evaluators then each used the CMT-FOM separately to evaluate 10 patient participants with genetically diagnosed CMT1A (the most common form of CMT) and their assessments were compared. Results indicated excellent inter-rater reliability. Researchers conclude that the CMT-FOM is a reliable clinical outcome assessment tool. CMT-FOM is important for natural history and clinical trial studies as it provides an evaluation based on functions that the patient performs in their hands and feet. It also allows a transition from the CMT Pediatric Scale (CMTPedS), a similar instrument for children with CMT.

The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME. Senderek J, Lassuthova P, Kabzińska D, Abreu L, Baets J, Beetz C, Braathen GJ, Brenner D, Dalton J, Dankwa L, Deconinck T, De Jonghe P, Dräger B, Eggermann K, Ellis M, Fischer C, Stojkovic T, Herrmann DN, Horvath R, Høyer H, Iglseder S, Kennerson M, Kinslechner K, Kohler JN, Kurth I, Laing NG, Lamont PJ, Wolfgang N L, Ludolph A, Marques W Jr, Nicholson G, Ong R, Petri S, Ravenscroft G, Rebelo A, Ricci G, Rudnik-Schöneborn S, Schirmacher A, Schlotter-Weigel B, Schoels L, Schüle R, Synofzik M, Francou B, Strom TM, Wagner J, Walk D, Wanschitz J, Weinmann D, Weishaupt J, Wiessner M, Windhager R, Young P, Züchner S, Toegel S, Seeman P, Kochański A, Auer-Grumbach M. Neurology. 2020 Dec 15;95(24):e3163-e3179. doi: 10.1212/WNL.0000000000011132. Epub 2020 Nov 3.

Transmembrane protease serine 5: a novel Schwann cell plasma marker for CMT1A. Wang H, Davison M, Wang K, Xia TH, Kramer M, Call K, Luo J, Wu X, Zuccarino R, Bacon C, Bai Y, Moran JJ, Gutmann L, Feely SME, Grider T, Rossor AM, Reilly MM, Svaren J, Shy ME. Ann Clin Transl Neurol. 2020 Jan;7(1):69-82. doi: 10.1002/acn3.50965. Epub 2019 Dec 12.

Validation of the Italian version of the Charcot-Marie-Tooth Health Index. Pisciotta C, Ciafaloni E, Zuccarino R, Calabrese D, Saveri P, Fenu S, Tramacere I, Genovese F, Dilek N, Johnson NE, Heatwole C, Herrmann DN, Pareyson D; ACT-CMT Study Group. J Peripher Nerv Syst. 2020 Sep;25(3):292-296. doi: 10.1111/jns.12397. Epub 2020 Jun 24.

Validation of the Italian version of the Charcot-Marie-Tooth disease Pediatric Scale. Zuccarino R, Prada V, Moroni I, Pagliano E, Foscan M, Robbiano G, Pisciotta C, Cornett K, Shy R, Schenone A, Pareyson D, Shy M, Burns J. J Peripher Nerv Syst. 2020 Jun;25(2):138-142. doi: 10.1111/jns.12383. Epub 2020 May 26.

A MT-ATP6 Mutation Causes a Slowly Progressive Myeloneuropathy. Bardakjian T, Scherer SS. J Neuromuscul Dis. 2019;6(3):385-387. doi: 10.3233/JND-190400.

A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs). Pareyson D, Stojkovic T, Reilly MM, Leonard-Louis S, Laurà M, Blake J, Parman Y, Battaloglu E, Tazir M, Bellatache M, Bonello-Palot N, Lévy N, Sacconi S, Guimarães-Costa R, Attarian S, Latour P, Solé G, Megarbane A, Horvath R, Ricci G, Choi BO, Schenone A, Gemelli C, Geroldi A, Sabatelli M, Luigetti M, Santoro L, Manganelli F, Quattrone A, Valentino P, Murakami T, Scherer SS, Dankwa L, Shy ME, Bacon CJ, Herrmann DN, Zambon A, Tramacere I, Pisciotta C, Magri S, Previtali SC, Bolino A. Ann Neurol. 2019 Jul;86(1):55-67. doi: 10.1002/ana.25500. Epub 2019 May 27.

A network biology approach to unraveling inherited axonopathies. Bis-Brewer DM, Danzi MC, Wuchty S, Züchner S. Sci Rep. 2019 Feb 8;9(1):1692. doi: 10.1038/s41598-018-37119-z.

A novel MFN2 mutation causes variable clinical severity in a multi-generational CMT2 family. Dankwa L, Richardson J, Motley WW, Scavina M, Courel S, Bardakjian T, Züchner S, Scherer SS. Neuromuscul Disord. 2019 Feb;29(2):134-137. doi: 10.1016/j.nmd.2018.12.008. Epub 2018 Dec 21.

A recurrent GARS mutation causes distal hereditary motor neuropathy. Lee DC, Meyer-Schuman R, Bacon C, Shy ME, Antonellis A, Scherer SS. J Peripher Nerv Syst. 2019 Dec;24(4):320-323. doi: 10.1111/jns.12353. Epub 2019 Nov 22.

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype. Cortese A, Lombardi R, Briani C, Callegari I, Benedetti L, Manganelli F, Luigetti M, Ferrari S, Clerici AM, Marfia GA, Rigamonti A, Carpo M, Fazio R, Corbo M, Mazzeo A, Giannini F, Cosentino G, Zardini E, Currò R, Gastaldi M, Vegezzi E, Alfonsi E, Berardinelli A, Kouton L, Manso C, Giannotta C, Doneddu P, Dacci P, Piccolo L, Ruiz M, Salvalaggio A, De Michelis C, Spina E, Topa A, Bisogni G, Romano A, Mariotto S, Mataluni G, Cerri F, Stancanelli C, Sabatelli M, Schenone A, Marchioni E, Lauria G, Nobile-Orazio E, Devaux J, Franciotta D. Neurol Neuroimmunol Neuroinflamm. 2019 Nov 21;7(1):e639. doi: 10.1212/NXI.0000000000000639. Print 2020 Jan.

Author Correction: Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, Ilyas M, Tribollet E, Tomaselli PJ, Devigili G, Callegari I, Versino M, Salpietro V, Efthymiou S, Kaski D, Wood NW, Andrade NS, Buglo E, Rebelo A, Rossor AM, Bronstein A, Fratta P, Marques WJ, Züchner S, Reilly MM, Houlden H. Nat Genet. 2019 May;51(5):920. doi: 10.1038/s41588-019-0422-y.

Balance impairment in pediatric charcot-marie-tooth disease. Estilow T, Glanzman AM, Burns J, Harrington A, Cornett K, Menezes MP, Shy R, Moroni I, Pagliano E, Pareyson D, Bhandari T, Muntoni F, Laurá M, Reilly MM, Finkel RS, Eichinger KJ, Herrmann DN, Troutman G, Bray P, Halaki M, Shy ME, Yum SW; CMTPedS STUDY GROUP. Muscle Nerve. 2019 Sep;60(3):242-249. doi: 10.1002/mus.26500. Epub 2019 May 15.

Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia. Wagner M, Osborn DPS, Gehweiler I, Nagel M, Ulmer U, Bakhtiari S, Amouri R, Boostani R, Hentati F, Hockley MM, Hölbling B, Schwarzmayr T, Karimiani EG, Kernstock C, Maroofian R, Müller-Felber W, Ozkan E, Padilla-Lopez S, Reich S, Reichbauer J, Darvish H, Shahmohammadibeni N, Tafakhori A, Vill K, Zuchner S, Kruer MC, Winkelmann J, Jamshidi Y, Schüle R. Nat Commun. 2019 Oct 21;10(1):4790. doi: 10.1038/s41467-019-12620-9.

Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, Ilyas M, Tribollet E, Tomaselli PJ, Devigili G, Callegari I, Versino M, Salpietro V, Efthymiou S, Kaski D, Wood NW, Andrade NS, Buglo E, Rebelo A, Rossor AM, Bronstein A, Fratta P, Marques WJ, Züchner S, Reilly MM, Houlden H. Nat Genet. 2019 Apr;51(4):649-658. doi: 10.1038/s41588-019-0372-4. Epub 2019 Mar 29.

Charcot-Marie-Tooth disease and related disorders: an evolving landscape. Laurá M, Pipis M, Rossor AM, Reilly MM. Curr Opin Neurol. 2019 Oct;32(5):641-650. doi: 10.1097/WCO.0000000000000735.

Clinical Presentation, Diagnosis and Treatment of TTR Amyloidosis. Kapoor M, Rossor AM, Laura M, Reilly MM. J Neuromuscul Dis. 2019;6(2):189-199. doi: 10.3233/JND-180371.

Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1. Kugathasan U, Evans MRB, Morrow JM, Sinclair CDJ, Thornton JS, Yousry TA, Hornemann T, Suriyanarayanan S, Owusu-Ansah K, Lauria G, Lombardi R, Polke JM, Wilson E, Bennett DLH, Houlden H, Hanna MG, Blake JC, Laura M, Reilly MM. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):895-906. doi: 10.1136/jnnp-2018-320198. Epub 2019 Apr 17.

FAHN/SPG35: a narrow phenotypic spectrum across disease classifications. Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, Hörtnagel K, Eckstein KN, Wiethoff S, Reichbauer J, Döbler-Neumann M, Krägeloh-Mann I, Auer-Grumbach M, Plecko B, Münchau A, Wilken B, Janauschek M, Giese AK, De Bleecker JL, Ortibus E, Debyser M, Lopez de Munain A, Pujol A, Bassi MT, D'Angelo MG, De Jonghe P, Züchner S, Bauer P, Schöls L, Schüle R. Brain. 2019 Jun 1;142(6):1561-1572. doi: 10.1093/brain/awz102.

Glutathione S-Transferase Regulates Mitochondrial Populations in Axons through Increased Glutathione Oxidation. Smith GA, Lin TH, Sheehan AE, Van der Goes van Naters W, Neukomm LJ, Graves HK, Bis-Brewer DM, Züchner S, Freeman MR. Neuron. 2019 Jul 3;103(1):52-65.e6. doi: 10.1016/j.neuron.2019.04.017. Epub 2019 May 14.

Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study. Tao F, Beecham GW, Rebelo AP, Blanton SH, Moran JJ, Lopez-Anido C, Svaren J, Abreu L, Rizzo D, Kirk CA, Wu X, Feely S, Verhamme C, Saporta MA, Herrmann DN, Day JW, Sumner CJ, Lloyd TE, Li J, Yum SW, Taroni F, Baas F, Choi BO, Pareyson D, Scherer SS, Reilly MM, Shy ME, Züchner S; Inherited Neuropathy Consortium. J Neuromuscul Dis. 2019;6(2):201-211. doi: 10.3233/JND-190377.

Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Pipis M, Rossor AM, Laura M, Reilly MM. Nat Rev Neurol. 2019 Nov;15(11):644-656. doi: 10.1038/s41582-019-0254-5. Epub 2019 Oct 3.

POLG mutations presenting as Charcot-Marie-Tooth disease. Phillips J, Courel S, Rebelo AP, Bis-Brewer DM, Bardakjian T, Dankwa L, Hamedani AG, Züchner S, Scherer SS. J Peripher Nerv Syst. 2019 Jun;24(2):213-218. doi: 10.1111/jns.12313. Epub 2019 Apr 10.

Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis. Kapoor M, Foiani M, Heslegrave A, Zetterberg H, Lunn MP, Malaspina A, Gillmore JD, Rossor AM, Reilly MM. J Peripher Nerv Syst. 2019 Dec;24(4):314-319. doi: 10.1111/jns.12350. Epub 2019 Oct 14.

Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies. Svaren J, Moran JJ, Wu X, Zuccarino R, Bacon C, Bai Y, Ramesh R, Gutmann L, Anderson DM, Pavelec D, Shy ME. Ann Neurol. 2019 Jun;85(6):887-898. doi: 10.1002/ana.25480. Epub 2019 Apr 22.

Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A. Tao F, Beecham GW, Rebelo AP, Svaren J, Blanton SH, Moran JJ, Lopez-Anido C, Morrow JM, Abreu L, Rizzo D, Kirk CA, Wu X, Feely S, Verhamme C, Saporta MA, Herrmann DN, Day JW, Sumner CJ, Lloyd TE, Li J, Yum SW, Taroni F, Baas F, Choi BO, Pareyson D, Scherer SS, Reilly MM, Shy ME, Züchner S; Inherited Neuropathy Consortium. Ann Neurol. 2019 Mar;85(3):316-330. doi: 10.1002/ana.25426.

Yield of next-generation neuropathy gene panels in axonal neuropathies. Lee DC, Dankwa L, Edmundson C, Cornblath DR, Scherer SS. J Peripher Nerv Syst. 2019 Dec;24(4):324-329. doi: 10.1111/jns.12356. Epub 2019 Nov 19.

A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family. Dankwa L, Richardson J, Motley WW, Züchner S, Scherer SS. J Peripher Nerv Syst. 2018 Mar;23(1):36-39. doi: 10.1111/jns.12248. Epub 2018 Feb 6.

Antisense oligonucleotides offer hope to patients with Charcot-Marie-Tooth disease type 1A. Shy ME. J Clin Invest. 2018 Jan 2;128(1):110-112. doi: 10.1172/JCI98617. Epub 2017 Dec 4.

Carpal tunnel syndrome in inherited neuropathies: A retrospective survey. Panosyan FB, Kirk CA, Marking D, Reilly MM, Scherer SS, Shy ME, Herrmann DN. Muscle Nerve. 2018 Mar;57(3):388-394. doi: 10.1002/mus.25742. Epub 2017 Jul 21.

Charcot Marie Tooth disease type 4J with complex central nervous system features. Orengo JP, Khemani P, Day JW, Li J, Siskind CE. Ann Clin Transl Neurol. 2018 Jan 22;5(2):222-225. doi: 10.1002/acn3.525. eCollection 2018 Feb.

Charcot-Marie-Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges. Jerath NU, Mankodi A, Crawford TO, Grunseich C, Baloui H, Nnamdi-Emeratom C, Schindler AB, Heiman-Patterson T, Chrast R, Shy ME. Muscle Nerve. 2018 May;57(5):749-755. doi: 10.1002/mus.25981. Epub 2017 Oct 24.

Clinical spectrum, treatment and outcome of children with suspected diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. Silwal A, Pitt M, Phadke R, Mankad K, Davison JE, Rossor A, DeVile C, Reilly MM, Manzur AY, Muntoni F, Munot P. Neuromuscul Disord. 2018 Sep;28(9):757-765. doi: 10.1016/j.nmd.2018.06.001. Epub 2018 Jun 12.

Development and validation of the Charcot-Marie-Tooth Disease Infant Scale. Mandarakas MR, Menezes MP, Rose KJ, Shy R, Eichinger K, Foscan M, Estilow T, Kennedy R, Herbert K, Bray P, Refshauge K, Ryan MM, Yiu EM, Farrar M, Sampaio H, Moroni I, Pagliano E, Pareyson D, Yum SW, Herrmann DN, Acsadi G, Shy ME, Burns J, Sanmaneechai O. Brain. 2018 Dec 1;141(12):3319-3330. doi: 10.1093/brain/awy280.

IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Tomaselli PJ, Horga A, Rossor AM, Jaunmuktane Z, Cortese A, Blake JC, Zarate-Lopez N, Houlden H, Reilly MM. Neuromuscul Disord. 2018 Dec;28(12):1012-1015. doi: 10.1016/j.nmd.2018.08.010. Epub 2018 Aug 29.

Insights into the genotype-phenotype correlation and molecular function of SLC25A46. Abrams AJ, Fontanesi F, Tan NBL, Buglo E, Campeanu IJ, Rebelo AP, Kornberg AJ, Phelan DG, Stark Z, Zuchner S. Hum Mutat. 2018 Dec;39(12):1995-2007. doi: 10.1002/humu.23639. Epub 2018 Sep 17.

Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brožková DŠ, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Am J Hum Genet. 2018;102(3):505-514. PMID: 29499166, PMCID: PMC5985288.

Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease. Shy M, Rebelo AP, Feely SM, Abreu LA, Tao F, Swenson A, Bacon C, Zuchner S. J Neurol Neurosurg Psychiatry. 2018 Mar;89(3):313-315. doi: 10.1136/jnnp-2017-315929. Epub 2017 Jul 28.

Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination. Hu B, McCollum M, Ravi V, Arpag S, Moiseev D, Castoro R, Mobley B, Burnette B, Siskind C, Day J, Yawn R, Feely S, Li Y, Yan Q, Shy M, Li J. Ann Neurol. 2018 Apr;83(4):756-770. doi: 10.1002/ana.25198. Epub 2018 Mar 30.

Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B. Bai Y, Wu X, Brennan KM, Wang DS, D'Antonio M, Moran J, Svaren J, Shy ME. Ann Clin Transl Neurol. 2018 Mar 10;5(4):445-455. doi: 10.1002/acn3.543. eCollection 2018 Apr.

Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies. Burnor E, Yang L, Zhou H, Patterson KR, Quinn C, Reilly MM, Rossor AM, Scherer SS, Lancaster E. Neurology. 2018 Jan 2;90(1):e31-e38. doi: 10.1212/WNL.0000000000004773. Epub 2017 Nov 29.

Neurofilament light, biomarkers, and Charcot-Marie-Tooth disease. Pareyson D, Shy ME. Neurology. 2018 Feb 6;90(6):257-259. doi: 10.1212/WNL.0000000000004936. Epub 2018 Jan 10.

Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Sandelius Å, Zetterberg H, Blennow K, Adiutori R, Malaspina A, Laura M, Reilly MM, Rossor AM. Neurology. 2018 Feb 6;90(6):e518-e524. doi: 10.1212/WNL.0000000000004932. Epub 2018 Jan 10.

Prevalence and orthopedic management of foot and ankle deformities in Charcot-Marie-Tooth disease. Laurá M, Singh D, Ramdharry G, Morrow J, Skorupinska M, Pareyson D, Burns J, Lewis RA, Scherer SS, Herrmann DN, Cullen N, Bradish C, Gaiani L, Martinelli N, Gibbons P, Pfeffer G, Phisitkul P, Wapner K, Sanders J, Flemister S, Shy ME, Reilly MM; Inherited Neuropathies Consortium. Muscle Nerve. 2018 Feb;57(2):255-259. doi: 10.1002/mus.25724. Epub 2017 Jul 7.

SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency. Rebelo AP, Saade D, Pereira CV, Farooq A, Huff TC, Abreu L, Moraes CT, Mnatsakanova D, Mathews K, Yang H, Schon EA, Zuchner S, Shy ME. Brain. 2018 Mar 1;141(3):662-672. doi: 10.1093/brain/awx369.

Somatotopic heat pain thresholds and intraepidermal nerve fibers in health. Davies JL, Engelstad JK Sr,, E Gove L, Linbo LK, Carter RE, Lynch C, Staff NP, Klein CJ, Dyck PJB, Herrmann DN, Dyck PJ. Muscle Nerve. 2018 Oct;58(4):509-516. doi: 10.1002/mus.26128. Epub 2018 Apr 20.

Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Abbott JA, Meyer-Schuman R, Lupo V, Feely S, Mademan I, Oprescu SN, Griffin LB, Alberti MA, Casasnovas C, Aharoni S, Basel-Vanagaite L, Züchner S, De Jonghe P, Baets J, Shy ME, Espinós C, Demeler B, Antonellis A, Francklyn C. Hum Mutat. 2018 Mar;39(3):415-432. doi: 10.1002/humu.23380. Epub 2017 Dec 26.

The Charcot-Marie-Tooth Functional Outcome Measure (CMT-FOM). Eichinger K, Burns J, Cornett K, Bacon C, Shepherd ML, Mountain J, Sowden J, Shy R, Shy ME, Herrmann DN. Neurology. 2018 Oct 9;91(15):e1381-e1384. doi: 10.1212/WNL.0000000000006323. Epub 2018 Sep 19.

The Charcot-Marie-Tooth Health Index: Evaluation of a Patient-Reported Outcome. Johnson NE, Heatwole C, Creigh P, McDermott MP, Dilek N, Hung M, Bounsanga J, Tang W, Shy ME, Herrmann DN. Ann Neurol. 2018 Aug;84(2):225-233. doi: 10.1002/ana.25282. Epub 2018 Aug 29.

Unique clinical and neurophysiologic profile of a cohort of children with CMTX3. Kanhangad M, Cornett K, Brewer MH, Nicholson GA, Ryan MM, Smith RL, Subramanian GM, Young HK, Züchner S, Kennerson ML, Burns J, Menezes MP. Neurology. 2018 May 8;90(19):e1706-e1710. doi: 10.1212/WNL.0000000000005479. Epub 2018 Apr 6.

Validation of MRC Centre MRI calf muscle fat fraction protocol as an outcome measure in CMT1A. Morrow JM, Evans MRB, Grider T, Sinclair CDJ, Thedens D, Shah S, Yousry TA, Hanna MG, Nopoulos P, Thornton JS, Shy ME, Reilly MM. Neurology. 2018 Sep 18;91(12):e1125-e1129. doi: 10.1212/WNL.0000000000006214. Epub 2018 Aug 17.

Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser. Saghira C, Bis DM, Stanek D, Strickland A, Herrmann DN, Reilly MM, Scherer SS, Shy ME; Inherited Neuropathy Consortium, Züchner S. Hum Mutat. 2018 May;39(5):635-642. doi: 10.1002/humu.23412. Epub 2018 Mar 14.

A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder. Tomaselli PJ, Rossor AM, Horga A, Laura M, Blake JC, Houlden H, Reilly MM. J Peripher Nerv Syst. 2017 Dec;22(4):460-463. doi: 10.1111/jns.12235. Epub 2017 Sep 11.

A human cellular model to study peripheral myelination and demyelinating neuropathies. Saporta MA, Shy ME. Brain. 2017 Apr 1;140(4):856-859. doi: 10.1093/brain/awx048.

A novel mutation in the FGD4 gene causing Charcot-Marie-Tooth disease. Zis P, Reilly MM, Rao DG, Tomaselli P, Rossor AM, Hadjivassiliou M. J Peripher Nerv Syst. 2017 Sep;22(3):224-225. doi: 10.1111/jns.12222.

A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Tsai PC, Soong BW, Mademan I, Huang YH, Liu CR, Hsiao CT, Wu HT, Liu TT, Liu YT, Tseng YT, Lin KP, Yang UC, Chung KW, Choi BO, Nicholson GA, Kennerson ML, Chan CC, De Jonghe P, Cheng TH, Liao YC, Züchner S, Baets J, Lee YC. Brain. 2017 May 1;140(5):1252-1266. doi: 10.1093/brain/awx058.

A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects. Ramdharry GM, Pollard AJ, Grant R, Dewar EL, Laurá M, Moore SA, Hallsworth K, Ploetz T, Trenell MI, Reilly MM. Disabil Rehabil. 2017 Aug;39(17):1753-1758. doi: 10.1080/09638288.2016.1211180. Epub 2016 Aug 16.

Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A. Fledrich R, Mannil M, Leha A, Ehbrecht C, Solari A, Pelayo-Negro AL, Berciano J, Schlotter-Weigel B, Schnizer TJ, Prukop T, Garcia-Angarita N, Czesnik D, Haberlová J, Mazanec R, Paulus W, Beissbarth T, Walter MC, Triaal C, Hogrel JY, Dubourg O, Schenone A, Baets J, De Jonghe P, Shy ME, Horvath R, Pareyson D, Seeman P, Young P, Sereda MW. J Neurol Neurosurg Psychiatry. 2017 Nov;88(11):941-952. doi: 10.1136/jnnp-2017-315721. Epub 2017 Aug 31.

CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis. Hengel H, Magee A, Mahanjah M, Vallat JM, Ouvrier R, Abu-Rashid M, Mahamid J, Schüle R, Schulze M, Krägeloh-Mann I, Bauer P, Züchner S, Sharkia R, Schöls L. Neurol Genet. 2017 Mar 22;3(2):e144. doi: 10.1212/NXG.0000000000000144. eCollection 2017 Apr.

Charcot-Marie-Tooth Disease Type 1A: Influence of Body Mass Index on Nerve Conduction Studies and on the Charcot-Marie-Tooth Examination Score. Jerath NU, Shy ME. J Clin Neurophysiol. 2017 Nov;34(6):508-511. doi: 10.1097/WNP.0000000000000415.

Charcot-Marie-Tooth disease type 1C: Clinical and electrophysiological findings for the c.334G>a (p.Gly112Ser) Litaf/Simple mutation. Jerath NU, Shy ME. Muscle Nerve. 2017 Dec;56(6):1092-1095. doi: 10.1002/mus.25600. Epub 2017 Apr 29.

Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1). Panosyan FB, Laura M, Rossor AM, Pisciotta C, Piscosquito G, Burns J, Li J, Yum SW, Lewis RA, Day J, Horvath R, Herrmann DN, Shy ME, Pareyson D, Reilly MM, Scherer SS; Inherited Neuropathies Consortium—Rare Diseases Clinical Research Network (INC-RDCRN). Neurology. 2017 Aug 29;89(9):927-935. doi: 10.1212/WNL.0000000000004296. Epub 2017 Aug 2.

Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Jacquier A, Delorme C, Belotti E, Juntas-Morales R, Solé G, Dubourg O, Giroux M, Maurage CA, Castellani V, Rebelo A, Abrams A, Züchner S, Stojkovic T, Schaeffer L, Latour P. Acta neuropathologica communications. 2017;5(1):55. PMID: 28709447, PMCID: PMC5513089.

Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Liao C, Ashley N, Diot A, Morten K, Phadwal K, Williams A, Fearnley I, Rosser L, Lowndes J, Fratter C, Ferguson DJ, Vay L, Quaghebeur G, Moroni I, Bianchi S, Lamperti C, Downes SM, Sitarz KS, Flannery PJ, Carver J, Dombi E, East D, Laura M, Reilly MM, Mortiboys H, Prevo R, Campanella M, Daniels MJ, Zeviani M, Yu-Wai-Man P, Simon AK, Votruba M, Poulton J. Neurology. 2017 Jan 10;88(2):131-142. doi: 10.1212/WNL.0000000000003491. Epub 2016 Dec 14.

Enhancements to the RDCRN Contact Registry for the Inherited Neuropathies Consortium. Hainline C, Rizzo D, Shy ME, Inherited Neuropathies Consortium, Rare Diseases Clinical Research Network Data Management and Coordinating Center. Poster presented at Peripheral Nerve Society Annual Meeting; Jul. 8-12, 2017; Sitges, Spain.

Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease. Horga A, Laurà M, Jaunmuktane Z, Jerath NU, Gonzalez MA, Polke JM, Poh R, Blake JC, Liu YT, Wiethoff S, Bettencourt C, Lunn MP, Manji H, Hanna MG, Houlden H, Brandner S, Züchner S, Shy M, Reilly MM. J Neurol Neurosurg Psychiatry. 2017 Jul;88(7):575-585. doi: 10.1136/jnnp-2016-315077. Epub 2017 May 13.

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R. Brain. 2017;140(12):3112-3127. PMID:29126212, PMCID: PMC5841036.

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression. Rocha N, Bulger DA, Frontini A, Titheradge H, Gribsholt SB, Knox R, Page M, Harris J, Payne F, Adams C, Sleigh A, Crawford J, Gjesing AP, Bork-Jensen J, Pedersen O, Barroso I, Hansen T, Cox H, Reilly M, Rossor A, Brown RJ, Taylor SI, McHale D, Armstrong M, Oral EA, Saudek V, O'Rahilly S, Maher ER, Richelsen B, Savage DB, Semple RK. Elife. 2017 Apr 19;6:e23813. doi: 10.7554/eLife.23813.

Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease. Kalmar B, Innes A, Wanisch K, Kolaszynska AK, Pandraud A, Kelly G, Abramov AY, Reilly MM, Schiavo G, Greensmith L. Hum Mol Genet. 2017 Sep 1;26(17):3313-3326. doi: 10.1093/hmg/ddx216.

Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT. Tomaselli PJ, Rossor AM, Horga A, Jaunmuktane Z, Carr A, Saveri P, Piscosquito G, Pareyson D, Laura M, Blake JC, Poh R, Polke J, Houlden H, Reilly MM. Neurology. 2017 Apr 11;88(15):1445-1453. doi: 10.1212/WNL.0000000000003819. Epub 2017 Mar 10.

Natural history of Charcot-Marie-Tooth disease during childhood. Cornett KMD, Menezes MP, Shy RR, Moroni I, Pagliano E, Pareyson D, Estilow T, Yum SW, Bhandari T, Muntoni F, Laura M, Reilly MM, Finkel RS, Eichinger KJ, Herrmann DN, Bray P, Halaki M, Shy ME, Burns J; CMTPedS Study Group. Ann Neurol. 2017 Sep;82(3):353-359. doi: 10.1002/ana.25009.

Novel mutations in dystonin provide clues to the pathomechanisms of HSAN-VI. Manganelli F, Parisi S, Nolano M, Tao F, Paladino S, Pisciotta C, Tozza S, Nesti C, Rebelo AP, Provitera V, Santorelli FM, Shy ME, Russo T, Zuchner S, Santoro L. Neurology. 2017 May 30;88(22):2132-2140. doi: 10.1212/WNL.0000000000003992. Epub 2017 May 3.

PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia. Ozes B, Karagoz N, Schüle R, Rebelo A, Sobrido MJ, Harmuth F, Synofzik M, Pascual SIP, Colak M, Ciftci-Kavaklioglu B, Kara B, Ordóñez-Ugalde A, Quintáns B, Gonzalez MA, Soysal A, Zuchner S, Battaloglu E. Clin Genet. 2017 Nov;92(5):534-539. doi: 10.1111/cge.13008. Epub 2017 Apr 19.

PMP22 exon 4 deletion causes ER retention of PMP22 and a gain-of-function allele in CMT1E. Wang DS, Wu X, Bai Y, Zaidman C, Grider T, Kamholz J, Lupski JR, Connolly AM, Shy ME. Ann Clin Transl Neurol. 2017 Mar 12;4(4):236-245. doi: 10.1002/acn3.395. eCollection 2017 Apr.

Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene. Rossor AM, Morrow JM, Polke JM, Murphy SM, Houlden H; INC-RDCRC, Laura M, Manji H, Blake J, Reilly MM. Neuromuscul Disord. 2017 Jan;27(1):50-56. doi: 10.1016/j.nmd.2016.10.001. Epub 2016 Oct 8.

Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias. Bis DM, Schüle R, Reichbauer J, Synofzik M, Rattay TW, Soehn A, de Jonghe P, Schöls L, Züchner S. Mol Genet Genomic Med. 2017 Apr 5;5(3):280-286. doi: 10.1002/mgg3.285. eCollection 2017 May.

A novel missense mutation of CMT2P alters transcription machinery. Hu B, Arpag S, Zuchner S, Li J. Ann Neurol. 2016 Dec;80(6):834-845. doi: 10.1002/ana.24776. Epub 2016 Sep 27.

A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. J Peripher Nerv Syst. 2016 Mar;21(1):33-7. doi: 10.1111/jns.12158.

Characterizing the molecular phenotype of an Atp7a(T985I) conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX). Perez-Siles G, Grant A, Ellis M, Ly C, Kidambi A, Khalil M, Llanos RM, Fontaine SL, Strickland AV, Züchner S, Bermeo S, Neist E, Brennan-Speranza TC, Takata RI, Speck-Martins CE, Mercer JF, Nicholson GA, Kennerson ML. Metallomics. 2016 Sep 1;8(9):981-92. doi: 10.1039/c6mt00082g. Epub 2016 Jun 13.

Charcot-marie-tooth disease type 1X in women: Electrodiagnostic findings. Jerath NU, Gutmann L, Reddy CG, Shy ME. Muscle Nerve. 2016 Oct;54(4):728-32. doi: 10.1002/mus.25077. Epub 2016 Jul 4.

Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region. Vallat JM, Nizon M, Magee A, Isidor B, Magy L, Péréon Y, Richard L, Ouvrier R, Cogné B, Devaux J, Zuchner S, Mathis S. J Neuropathol Exp Neurol. 2016 Dec 1;75(12):1155-1159. doi: 10.1093/jnen/nlw093.

Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Rebelo AP, Abrams AJ, Cottenie E, Horga A, Gonzalez M, Bis DM, Sanchez-Mejias A, Pinto M, Buglo E, Markel K, Prince J, Laura M, Houlden H, Blake J, Woodward C, Sweeney MG, Holton JL, Hanna M, Dallman JE, Auer-Grumbach M, Reilly MM, Zuchner S. Am J Hum Genet. 2016; 98(4):597-614. PMID: 27040688, PMCID: PMC4833435.

De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease. Motley WW, Palaima P, Yum SW, Gonzalez MA, Tao F, Wanschitz JV, Strickland AV, Löscher WN, De Vriendt E, Koppi S, Medne L, Janecke AR, Jordanova A, Zuchner S, Scherer SS. Brain. 2016 Jun;139(Pt 6):1649-56. doi: 10.1093/brain/aww055. Epub 2016 Mar 23.

Gene therapy, CMT1X, and the inherited neuropathies. Shy ME. Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4552-4. doi: 10.1073/pnas.1604005113. Epub 2016 Apr 14.

LRSAM1 lessons. Shy M. Ann Neurol. 2016 Dec;80(6):821-822. doi: 10.1002/ana.24817.

MORC2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal signs. Albulym OM, Kennerson ML, Harms MB, Drew AP, Siddell AH, Auer-Grumbach M, Pestronk A, Connolly A, Baloh RH, Zuchner S, Reddel SW, Nicholson GA. Ann Neurol. 2016 Mar;79(3):419-27. doi: 10.1002/ana.24575. Epub 2016 Jan 13.

MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Morrow JM, Sinclair CD, Fischmann A, Machado PM, Reilly MM, Yousry TA, Thornton JS, Hanna MG. Lancet Neurol. 2016 Jan;15(1):65-77. doi: 10.1016/S1474-4422(15)00242-2. Epub 2015 Nov 6.

Multisystemic SYNE1 ataxia: confirming the high frequency and extending the mutational and phenotypic spectrum. Mademan I, Harmuth F, Giordano I, Timmann D, Magri S, Deconinck T, Claaßen J, Jokisch D, Genc G, Di Bella D, Romito S, Schüle R, Züchner S, Taroni F, Klockgether T, Schöls L, De Jonghe P, Bauer P, Consortium E, Baets J, Synofzik M. Brain. 2016 Aug;139(Pt 8):e46. doi: 10.1093/brain/aww115. Epub 2016 May 19.

Nerve conduction velocity in CMT1A: what else can we tell?. Manganelli F, Pisciotta C, Reilly MM, Tozza S, Schenone A, Fabrizi GM, Cavallaro T, Vita G, Padua L, Gemignani F, Laurà M, Hughes RA, Solari A, Pareyson D, Santoro L; CMT-TRIAAL and CMT-TRAUK Group. Eur J Neurol. 2016 Oct;23(10):1566-71. doi: 10.1111/ene.13079. Epub 2016 Jul 14.

Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease. Cornett KM, Menezes MP, Bray P, Halaki M, Shy RR, Yum SW, Estilow T, Moroni I, Foscan M, Pagliano E, Pareyson D, Laurá M, Bhandari T, Muntoni F, Reilly MM, Finkel RS, Sowden J, Eichinger KJ, Herrmann DN, Shy ME, Burns J; Inherited Neuropathies Consortium. JAMA Neurol. 2016 Jun 1;73(6):645-51. doi: 10.1001/jamaneurol.2016.0171.

Plasma neurofilament heavy chain is not a useful biomarker in Charcot-Marie-Tooth disease. Rossor AM, Lu CH, Petzold A, Malaspina A, Laura M, Greensmith L, Reilly MM. Muscle Nerve. 2016 Jun;53(6):972-5. doi: 10.1002/mus.25124. Epub 2016 Apr 27.

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies. Auer-Grumbach M, Toegel S, Schabhüttl M, Weinmann D, Chiari C, Bennett DLH, Beetz C, Klein D, Andersen PM, Böhme I, Fink-Puches R, Gonzalez M, Harms MB, Motley W, Reilly MM, Renner W, Rudnik-Schöneborn S, Schlotter-Weigel B, Themistocleous AC, Weishaupt JH, Ludolph AC, Wieland T, Tao F, Abreu L, Windhager R, Zitzelsberger M, Strom TM, Walther T, Scherer SS, Züchner S, Martini R, Senderek J. Am J Hum Genet. 2016 Sep 1;99(3):607-623. doi: 10.1016/j.ajhg.2016.07.008.

Recent advances in the genetic neuropathies. Rossor AM, Tomaselli PJ, Reilly MM. Curr Opin Neurol. 2016 Oct;29(5):537-48. doi: 10.1097/WCO.0000000000000373.

Rydel-Seiffer fork revisited: Beyond a simple case of black and white. Panosyan FB, Mountain JM, Reilly MM, Shy ME, Herrmann DN. Neurology. 2016 Aug 16;87(7):738-40. doi: 10.1212/WNL.0000000000002991. Epub 2016 Jul 13.

SIGMAR1 mutation associated with autosomal recessive Silver-like syndrome. Horga A, Tomaselli PJ, Gonzalez MA, Laurà M, Muntoni F, Manzur AY, Hanna MG, Blake JC, Houlden H, Züchner S, Reilly MM. Neurology. 2016 Oct 11;87(15):1607-1612. doi: 10.1212/WNL.0000000000003212. Epub 2016 Sep 14.

SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. Synofzik M, Smets K, Mallaret M, Di Bella D, Gallenmüller C, Baets J, Schulze M, Magri S, Sarto E, Mustafa M, Deconinck T, Haack T, Züchner S, Gonzalez M, Timmann D, Stendel C, Klopstock T, Durr A, Tranchant C, Sturm M, Hamza W, Nanetti L, Mariotti C, Koenig M, Schöls L, Schüle R, de Jonghe P, Anheim M, Taroni F, Bauer P. Brain. 2016 May;139(Pt 5):1378-93. doi: 10.1093/brain/aww079. Epub 2016 Apr 17.

Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4). Piscosquito G, Saveri P, Magri S, Ciano C, Gandioli C, Morbin M, Bella DD, Moroni I, Taroni F, Pareyson D. J Peripher Nerv Syst. 2016 Sep;21(3):142-9. doi: 10.1111/jns.12175.

Severe axonal Charcot-Marie-Tooth disease with proximal weakness caused by de novo mutation in the MORC2 gene. Laššuthová P, Šafka Brožková D, Krůtová M, Mazanec R, Züchner S, Gonzalez MA, Seeman P. Brain. 2016 Apr;139(Pt 4):e26. doi: 10.1093/brain/awv411. Epub 2016 Feb 11.

Severe axonal neuropathy is a late manifestation of SPG11. Manole A, Chelban V, Haridy NA, Hamed SA, Berardo A, Reilly MM, Houlden H. J Neurol. 2016 Nov;263(11):2278-2286. doi: 10.1007/s00415-016-8254-5. Epub 2016 Aug 20.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Total contact cast wall load in patients with a plantar forefoot ulcer and diabetes. Begg L, McLaughlin P, Vicaretti M, Fletcher J, Burns J. J Foot Ankle Res. 2016 Jan 7;9:2. doi: 10.1186/s13047-015-0119-0. eCollection 2016.

Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3. Brewer MH, Chaudhry R, Qi J, Kidambi A, Drew AP, Menezes MP, Ryan MM, Farrar MA, Mowat D, Subramanian GM, Young HK, Zuchner S, Reddel SW, Nicholson GA, Kennerson ML. PLoS Genet. 2016 Jul 20;12(7):e1006177. doi: 10.1371/journal.pgen.1006177. eCollection 2016 Jul.

A new prion disease: relationship with central and peripheral amyloidoses. Mead S, Reilly MM. Nature reviews. Neurology. Feb 2015;11(2):90-97. PMID: 25623792.

A novel AARS mutation in a family with dominant myeloneuropathy. Motley WW, Griffin LB, Mademan I, Baets J, De Vriendt E, De Jonghe P, Antonellis A, Jordanova A, Scherer SS. Neurology. 2015 May 19;84(20):2040-7. doi: 10.1212/WNL.0000000000001583. Epub 2015 Apr 22.

A practical approach to the genetic neuropathies. Rossor AM, Evans MR, Reilly MM. Pract Neurol. 2015 Jun;15(3):187-98. doi: 10.1136/practneurol-2015-001095. Epub 2015 Apr 21.

Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation. Thal DR, Züchner S, Gierer S, Schulte C, Schöls L, Schüle R, Synofzik M. Int J Mol Sci. 2015 Oct 21;16(10):25050-66. doi: 10.3390/ijms161025050.

Absence of Dystrophin Related Protein-2 disrupts Cajal bands in a patient with Charcot-Marie-Tooth disease. Brennan KM, Bai Y, Pisciotta C, Wang S, Feely SM, Hoegger M, Gutmann L, Moore SA, Gonzalez M, Sherman DL, Brophy PJ, Züchner S, Shy ME. Neuromuscul Disord. 2015 Oct;25(10):786-93. doi: 10.1016/j.nmd.2015.07.001. Epub 2015 Jul 7.

Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation. Tétreault M, Gonzalez M, Dicaire MJ, Allard P, Gehring K, Leblanc D, Leclerc N, Schondorf R, Mathieu J, Zuchner S, Brais B. Brain. 2015 Jun;138(Pt 6):1477-83. doi: 10.1093/brain/awv074. Epub 2015 Mar 28.

Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. Coutelier M, Goizet C, Durr A, Habarou F, Morais S, Dionne-Laporte A, Tao F, Konop J, Stoll M, Charles P, Jacoupy M, Matusiak R, Alonso I, Tallaksen C, Mairey M, Kennerson M, Gaussen M, Schule R, Janin M, Morice-Picard F, Durand CM, Depienne C, Calvas P, Coutinho P, Saudubray JM, Rouleau G, Brice A, Nicholson G, Darios F, Loureiro JL, Zuchner S, Ottolenghi C, Mochel F, Stevanin G. Brain. 2015 Aug;138(Pt 8):2191-205. doi: 10.1093/brain/awv143. Epub 2015 May 29.

An observational study of asymmetry in CMT1A. Pelayo-Negro AL, Carr AS, Laura M, Skorupinska M, Reilly MM. J Neurol Neurosurg Psychiatry. 2015 May;86(5):589-90. doi: 10.1136/jnnp-2014-309096. Epub 2014 Oct 13.

Axonal Charcot-Marie-Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties. Saporta MA, Dang V, Volfson D, Zou B, Xie XS, Adebola A, Liem RK, Shy M, Dimos JT. Exp Neurol. 2015 Jan;263:190-9. doi: 10.1016/j.expneurol.2014.10.005. Epub 2014 Oct 30.

CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. Fridman V, Bundy B, Reilly MM, Pareyson D, Bacon C, Burns J, Day J, Feely S, Finkel RS, Grider T, Kirk CA, Herrmann DN, Laurá M, Li J, Lloyd T, Sumner CJ, Muntoni F, Piscosquito G, Ramchandren S, Shy R, Siskind CE, Yum SW, Moroni I, Pagliano E, Zuchner S, Scherer SS, Shy ME; Inherited Neuropathies Consortium. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):873-8. doi: 10.1136/jnnp-2014-308826. Epub 2014 Nov 27.

Coexistence of a T118M PMP22 missense mutation and chromosome 17 (17p11.2-p12) deletion. Jerath NU, Kamholz J, Grider T, Harper A, Swenson A, Shy ME. Muscle Nerve. 2015 Nov;52(5):905-8. doi: 10.1002/mus.24713. Epub 2015 Jun 19.

Correlates of functional ankle instability in children and adolescents with Charcot-Marie-Tooth disease. Rose KJ, Hiller CE, Mandarakas M, Raymond J, Refshauge K, Burns J. J Foot Ankle Res. 2015 Nov 5;8:61. doi: 10.1186/s13047-015-0118-1. eCollection 2015.

Defects of mutant DNMT1 are linked to a spectrum of neurological disorders. Baets J, Duan X, Wu Y, Smith G, Seeley WW, Mademan I, McGrath NM, Beadell NC, Khoury J, Botuyan MV, Mer G, Worrell GA, Hojo K, DeLeon J, Laura M, Liu YT, Senderek J, Weis J, Van den Bergh P, Merrill SL, Reilly MM, Houlden H, Grossman M, Scherer SS, De Jonghe P, Dyck PJ, Klein CJ. Brain. 2015 Apr;138(Pt 4):845-61. doi: 10.1093/brain/awv010. Epub 2015 Feb 11.

Defining disability: development and validation of a mobility-Disability Severity Index (mDSI) in Charcot-Marie-tooth disease. Ramchandren S, Shy M, Feldman E, Carlos R, Siskind C. J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):635-9. doi: 10.1136/jnnp-2013-307390. Epub 2014 Aug 25.

Demyelinating CMT--what's known, what's new and what's in store?. Brennan KM, Bai Y, Shy ME. Neurosci Lett. 2015 Jun 2;596:14-26. doi: 10.1016/j.neulet.2015.01.059. Epub 2015 Jan 24.

Detection of copy number variation by SNP-allelotyping. Parker B, Alexander R, Wu X, Feely S, Shy M, Schnetz-Boutaud N, Li J. J Neurogenet. 2015 Mar;29(1):4-7. doi: 10.3109/01677063.2014.923884. Epub 2014 Jun 2.

Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia. Schmidt WM, Rutledge SL, Schüle R, Mayerhofer B, Züchner S, Boltshauser E, Bittner RE. Am J Hum Genet. 2015 Dec 3;97(6):855-61. doi: 10.1016/j.ajhg.2015.10.011. Epub 2015 Nov 12.

Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome. Whittaker RG, Herrmann DN, Bansagi B, Hasan BA, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R, Lochmüller H. Neurology. 2015 Dec 1;85(22):1964-71. doi: 10.1212/WNL.0000000000002185. Epub 2015 Oct 30.

Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy. Gonzaga-Jauregui C, Harel T, Gambin T, Kousi M, Griffin LB, Francescatto L, Ozes B, Karaca E, Jhangiani SN, Bainbridge MN, Lawson KS, Pehlivan D, Okamoto Y, Withers M, Mancias P, Slavotinek A, Reitnauer PJ, Goksungur MT, Shy M, Crawford TO, Koenig M, Willer J, Flores BN, Pediaditrakis I, Us O, Wiszniewski W, Parman Y, Antonellis A, Muzny DM; Baylor-Hopkins Center for Mendelian Genomics, Katsanis N, Battaloglu E, Boerwinkle E, Gibbs RA, Lupski JR. Cell Rep. 2015 Aug 18;12(7):1169-83. doi: 10.1016/j.celrep.2015.07.023. Epub 2015 Aug 6.

Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC). Brain. 2015 Nov;138(Pt 11):3180-92. doi: 10.1093/brain/awv241. Epub 2015 Aug 25.

Hereditary Neuropathies in Late Childhood and Adolescence. Brennan K, Shy M. In: Darras B, Jones H, Ryan M, De Vivo D, eds. Neuromuscular Disorders of Infancy, Childhood and Adolescence: A Clinicians Approach. 2nd ed: Elsevier Inc; 2015:319-339.

Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies. Jerath NU, Shy ME. Biochim Biophys Acta. 2015 Apr;1852(4):667-78. doi: 10.1016/j.bbadis.2014.07.031. Epub 2014 Aug 6.

Inclusion body myositis and sarcoid myopathy: coincidental occurrence or associated diseases. Sanmaneechai O, Swenson A, Gerke AK, Moore SA, Shy ME. Neuromuscul Disord. Apr 2015;25(4):297-300. PMID: 25599912

Innovative genomic collaboration using the GENESIS (GEM.app) platform. Gonzalez M, Falk MJ, Gai X, Postrel R, Schüle R, Zuchner S. Hum Mutat. 2015 Oct;36(10):950-6. doi: 10.1002/humu.22836. Epub 2015 Aug 12.

Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Safka Brozkova D, Deconinck T, Griffin LB, Ferbert A, Haberlova J, Mazanec R, Lassuthova P, Roth C, Pilunthanakul T, Rautenstrauss B, Janecke AR, Zavadakova P, Chrast R, Rivolta C, Zuchner S, Antonellis A, Beg AA, De Jonghe P, Senderek J, Seeman P, Baets J. Brain. 2015 Aug;138(Pt 8):2161-72. doi: 10.1093/brain/awv158. Epub 2015 Jun 13.

MFN2 deletion of exons 7 and 8: founder mutation in the UK population. Carr AS, Polke JM, Wilson J, Pelayo-Negro AL, Laura M, Nanji T, Holt J, Vaughan J, Rankin J, Sweeney MG, Blake J, Houlden H, Reilly MM. J Peripher Nerv Syst. 2015 Jun;20(2):67-71. doi: 10.1111/jns.12117.

Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1. Strickland AV, Schabhüttl M, Offenbacher H, Synofzik M, Hauser NS, Brunner-Krainz M, Gruber-Sedlmayr U, Moore SA, Windhager R, Bender B, Harms M, Klebe S, Young P, Kennerson M, Garcia AS, Gonzalez MA, Züchner S, Schule R, Shy ME, Auer-Grumbach M. J Neurol. 2015 Sep;262(9):2124-34. doi: 10.1007/s00415-015-7727-2. Epub 2015 Jun 24.

Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schüle R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Németh AH, Carelli V, Huang T, Zuchner S, Dallman JE. Nat Genet. 2015 Aug;47(8):926-32. doi: 10.1038/ng.3354. Epub 2015 Jul 13.

Novel HSAN1 mutation in serine palmitoyltransferase resides at a putative phosphorylation site that is involved in regulating substrate specificity. Ernst D, Murphy SM, Sathiyanadan K, Wei Y, Othman A, Laurá M, Liu YT, Penno A, Blake J, Donaghy M, Houlden H, Reilly MM, Hornemann T. Neuromolecular Med. 2015 Mar;17(1):47-57. doi: 10.1007/s12017-014-8339-1. Epub 2015 Jan 8.

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. Scoto M, Rossor AM, Harms MB, Cirak S, Calissano M, Robb S, Manzur AY, Martínez Arroyo A, Rodriguez Sanz A, Mansour S, Fallon P, Hadjikoumi I, Klein A, Yang M, De Visser M, Overweg-Plandsoen WC, Baas F, Taylor JP, Benatar M, Connolly AM, Al-Lozi MT, Nixon J, de Goede CG, Foley AR, Mcwilliam C, Pitt M, Sewry C, Phadke R, Hafezparast M, Chong WK, Mercuri E, Baloh RH, Reilly MM, Muntoni F. Neurology. 2015 Feb 17;84(7):668-79. doi: 10.1212/WNL.0000000000001269. Epub 2015 Jan 21.

Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient. McColgan P, Viegas S, Gandhi S, Bull K, Tudor R, Sheikh F, Pinney J, Fontana M, Rowczenio D, Gillmore JD, Gilbertson JA, Whelan CJ, Shah S, Jaunmuktane Z, Holton JL, Schott JM, Werring DJ, Hawkins PN, Reilly MM. J Neurol. 2015 Jan;262(1):228-34. doi: 10.1007/s00415-014-7594-2. Epub 2014 Dec 9.

Peripheral Neuropathies. Saporta M, Shy M. In: Zigmond M, Coyle J, Rowland L, eds. Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders. 1st ed: Academic Press; 2015:167-188.

Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Brain. Feb 2015;138(Pt 2):293-310. PMID: 25497877, PMCID: PMC4306822.

Progressive Lower Extremity Weakness and Axonal Sensorimotor Polyneuropathy from a Mutation in KIF5A (c.611G>A;p.Arg204Gln). Jerath NU, Grider T, Shy ME. Case Rep Genet. 2015;2015:496053. doi: 10.1155/2015/496053. Epub 2015 Oct 12.

Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation. Jerath NU, Crockett CD, Moore SA, Shy ME, Weihl CC, Chou TF, Grider T, Gonzalez MA, Zuchner S, Swenson A. Case Rep Genet. 2015;2015:239167. doi: 10.1155/2015/239167. Epub 2015 Mar 23.

Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E. Pisciotta C, Bai Y, Brennan KM, Wu X, Grider T, Feely S, Wang S, Moore S, Siskind C, Gonzalez M, Zuchner S, Shy ME. Neurology. 2015 Jul 21;85(3):228-34. doi: 10.1212/WNL.0000000000001773. Epub 2015 Jun 24.

Small nerve fiber involvement in CMT1A. Nolano M, Manganelli F, Provitera V, et al. Neurology. 2015;84(4):407-414. PMID: 25540311, PMCID: PMC4336000.

The Matchmaker Exchange: a platform for rare disease gene discovery. Philippakis AA, Azzariti DR, Beltran S, Brookes AJ, Brownstein CA, Brudno M, Brunner HG, Buske OJ, Carey K, Doll C, Dumitriu S, Dyke SO, den Dunnen JT, Firth HV, Gibbs RA, Girdea M, Gonzalez M, Haendel MA, Hamosh A, Holm IA, Huang L, Hurles ME, Hutton B, Krier JB, Misyura A, Mungall CJ, Paschall J, Paten B, Robinson PN, Schiettecatte F, Sobreira NL, Swaminathan GJ, Taschner PE, Terry SF, Washington NL, Züchner S, Boycott KM, Rehm HL. Hum Mutat. 2015 Oct;36(10):915-21. doi: 10.1002/humu.22858.

Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. Carr AS, Pelayo-Negro AL, Jaunmuktane Z, Scalco RS, Hutt D, Evans MR, Heally E, Brandner S, Holton J, Blake J, Whelan CJ, Wechalekar AD, Gillmore JD, Hawkins PN, Reilly MM. Neuromuscul Disord. 2015 Jun;25(6):511-5. doi: 10.1016/j.nmd.2015.02.001. Epub 2015 Feb 14.

Tremor in Charcot-Marie-Tooth disease: No evidence of cerebellar dysfunction. Saifee TA, Parees I, Kassavetis P, et al. Clin Neurophysiol. Sep 2015;126(9):1817-1824. PMID: 25641441.

Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach. Zimoń M, Battaloğlu E, Parman Y, Erdem S, Baets J, De Vriendt E, Atkinson D, Almeida-Souza L, Deconinck T, Ozes B, Goossens D, Cirak S, Van Damme P, Shboul M, Voit T, Van Maldergem L, Dan B, El-Khateeb MS, Guergueltcheva V, Lopez-Laso E, Goemans N, Masri A, Züchner S, Timmerman V, Topaloğlu H, De Jonghe P, Jordanova A. Neurogenetics. 2015 Jan;16(1):33-42. doi: 10.1007/s10048-014-0422-0. Epub 2014 Sep 18.

Update on Charcot-Marie-Tooth disease. Gutmann L, Shy M. Curr Opin Neurol. 2015 Oct;28(5):462-7. doi: 10.1097/WCO.0000000000000237.

A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease. Gonzalez MA, Feely SM, Speziani F, Strickland AV, Danzi M, Bacon C, Lee Y, Chou TF, Blanton SH, Weihl CC, Zuchner S, Shy ME. Brain. 2014 Nov;137(Pt 11):2897-902. doi: 10.1093/brain/awu224. Epub 2014 Aug 14.

A pilot study of proximal strength training in Charcot-Marie-Tooth disease. Ramdharry GM, Pollard A, Anderson C, Laurá M, Murphy SM, Dudziec M, Dewar EL, Hutton E, Grant R, Reilly MM. J Peripher Nerv Syst. 2014 Dec;19(4):328-32. doi: 10.1111/jns.12100.

An ¹⁸F-FDG PET study of cervical muscle in parkinsonian anterocollis. Revuelta GJ, Montilla J, Benatar M, Freeman A, Wichmann T, Jinnah HA, Delong MR, Factor SA. J Neurol Sci. 2014 May 15;340(1-2):174-7. doi: 10.1016/j.jns.2014.03.023. Epub 2014 Mar 18.

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation. Liu YT, Hersheson J, Plagnol V, Fawcett K, Duberley KE, Preza E, Hargreaves IP, Chalasani A, Laurá M, Wood NW, Reilly MM, Houlden H. J Neurol Neurosurg Psychiatry. 2014 May;85(5):493-8. doi: 10.1136/jnnp-2013-306483. Epub 2013 Nov 11.

Charcot-Marie-Tooth Disease. Rossor AR, MM. In: Hilton-Jones D, Turner M, eds. Oxford Textbook of Neuromuscular Disorders. Oxford, UK: Oxford University Press; 2014:61-74.

Effect of pain in pediatric inherited neuropathies. Ramchandren S, Jaiswal M, Feldman E, Shy M. Neurology. 2014 Mar 4;82(9):793-7. doi: 10.1212/WNL.0000000000000173. Epub 2014 Jan 29.

Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Liu YT, Laurá M, Hersheson J, Horga A, Jaunmuktane Z, Brandner S, Pittman A, Hughes D, Polke JM, Sweeney MG, Proukakis C, Janssen JC, Auer-Grumbach M, Zuchner S, Shields KG, Reilly MM, Houlden H. Neurology. 2014 Aug 12;83(7):612-9. doi: 10.1212/WNL.0000000000000691. Epub 2014 Jul 9.

Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Timmerman V, Strickland AV, Züchner S. Genes (Basel). 2014 Jan 22;5(1):13-32. doi: 10.3390/genes5010013.

Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2. Brewer MH, Ma KH, Beecham GW, Gopinath C, Baas F, Choi BO, Reilly MM, Shy ME, Züchner S, Svaren J, Antonellis A. Hum Mol Genet. 2014 Oct 1;23(19):5171-87. doi: 10.1093/hmg/ddu240. Epub 2014 May 15.

Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations. Griffin LB, Sakaguchi R, McGuigan D, Gonzalez MA, Searby C, Züchner S, Hou YM, Antonellis A. Hum Mutat. 2014 Nov;35(11):1363-71. doi: 10.1002/humu.22681.

Improved anatomical reproducibility in quantitative lower-limb muscle MRI. Fischmann A, Morrow JM, Sinclair CD, Reilly MM, Hanna MG, Yousry T, Thornton JS. J Magn Reson Imaging. 2014 Apr;39(4):1033-8. doi: 10.1002/jmri.24220. Epub 2013 Oct 7.

Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish. Wen R, Dallman JE, Li Y, Züchner SL, Vance JM, Peričak-Vance MA, Lam BL. Adv Exp Med Biol. 2014;801:543-50. doi: 10.1007/978-1-4614-3209-8_69.

Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. Esteves T, Durr A, Mundwiller E, et al. Am J Hum Genet. Feb 6 2014;94(2):268-277. PMID: 24388663, PMCID: PMC3928657.

Motor protein mutations cause a new form of hereditary spastic paraplegia. Caballero Oteyza A, Battaloglu E, Ocek L, et al. Neurology. Jun 3 2014;82(22):2007-2016. PMID: 24808017, PMCID: PMC4105256.

Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa. Lam BL, Züchner SL, Dallman J, Wen R, Alfonso EC, Vance JM, Peričak-Vance MA. Adv Exp Med Biol. 2014;801:165-70. doi: 10.1007/978-1-4614-3209-8_21.

Natural History and Biomarkers in Hereditary Sensory Neuropathy Type 1. Fridman V, Oaklander AL, David WS, et al. Muscle Nerve. Jul 10 2014. PMID: 25042817.

Normative reference values for lower limb joint range, bone torsion, and alignment in children aged 4-16 years. Mudge AJ, Bau KV, Purcell LN, Wu JC, Axt MW, Selber P, Burns J. J Pediatr Orthop B. 2014 Jan;23(1):15-25. doi: 10.1097/BPB.0b013e328364220a.

Observational study of spinal muscular atrophy type I and implications for clinical trials. Finkel RS, McDermott MP, Kaufmann P, Darras BT, Chung WK, Sproule DM, Kang PB, Foley AR, Yang ML, Martens WB, Oskoui M, Glanzman AM, Flickinger J, Montes J, Dunaway S, O'Hagen J, Quigley J, Riley S, Benton M, Ryan PA, Montgomery M, Marra J, Gooch C, De Vivo DC. Neurology. 2014 Aug 26;83(9):810-7. doi: 10.1212/WNL.0000000000000741. Epub 2014 Jul 30.

PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Synofzik M, Gonzalez MA, Lourenco CM, et al. Brain. Jan 2014;137(Pt 1):69-77. PMID: 24355708, PMCID: PMC3891450.

Pain and small fiber function in Charcot-Marie-Tooth disease type 1A. Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM. Muscle Nerve. 2014 Sep;50(3):366-71. doi: 10.1002/mus.24169. Epub 2014 May 15.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia. Horga A, Pitceathly RD, Blake JC, Woodward CE, Zapater P, Fratter C, Mudanohwo EE, Plant GT, Houlden H, Sweeney MG, Hanna MG, Reilly MM. Brain. 2014 Dec;137(Pt 12):3200-12. doi: 10.1093/brain/awu279. Epub 2014 Oct 3.

Prospective Study of Muscle Cramps in Charcot-Marie- Tooth Disease. Johnson NE, Sowden J, Dilek N, et al. Muscle Nerve. Jul 5 2014. PMID: 25042364.

Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases. Dortch RD, Dethrage LM, Gore JC, Smith SA, Li J. Neurology. 2014 Oct 21;83(17):1545-53. doi: 10.1212/WNL.0000000000000919. Epub 2014 Sep 24.

Psychometrics evaluation of Charcot-Marie-Tooth Neuropathy Score (CMTNSv2) second version, using Rasch analysis. Sadjadi R, Reilly MM, Shy ME, Pareyson D, Laura M, Murphy S, Feely SM, Grider T, Bacon C, Piscosquito G, Calabrese D, Burns TM. J Peripher Nerv Syst. 2014 Sep;19(3):192-6. doi: 10.1111/jns.12084.

Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier. Bonifert T, Karle KN, Tonagel F, et al. Brain. 2014;137(Pt 8):2164-2177. PMID: 24970096, PMCID: PMC4107747.

Quality-of-life in Charcot-Marie-Tooth disease: the patient's perspective. Johnson NE, Heatwole CR, Dilek N, Sowden J, Kirk CA, Shereff D, Shy ME, Herrmann DN; Inherited Neuropathies Consortium. Neuromuscul Disord. 2014 Nov;24(11):1018-23. doi: 10.1016/j.nmd.2014.06.433. Epub 2014 Jun 27.

Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Morrow JM, Sinclair CD, Fischmann A, et al. Eur Radiol. Jul 2014;24(7):1610-1620. PMID: 24748539, PMCID: PMC4046083.

Sequencing of Charcot-Marie-Tooth disease genes in a toxic polyneuropathy. Beutler AS, Kulkarni AA, Kanwar R, et al. Ann Neurol. Nov 2014;76(5):727-737. PMID: 25164601, PMCID: PMC4388308.

Smoking and Parkinson disease: where there is smoke there may not be fire. Hershey LA, Perlmutter JS. Neurology. 2014 Oct 14;83(16):1392-3. doi: 10.1212/WNL.0000000000000896. Epub 2014 Sep 12.

Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Am J Hum Genet. 2014 Sep 4;95(3):332-9. doi: 10.1016/j.ajhg.2014.08.007.

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, Jungbluth H, Lim MJ, Lin JP, Megarbane A, Urtizberea JA, Shah AH, Antony J, Webster R, Broomfield A, Ng J, Mathew AA, O'Byrne JJ, Forman E, Scoto M, Prasad M, O'Brien K, Olpin S, Oppenheim M, Hargreaves I, Land JM, Wang MX, Carpenter K, Horvath R, Straub V, Lek M, Gold W, Farrell MO, Brandner S, Phadke R, Matsubara K, McGarvey ML, Scherer SS, Baxter PS, King MD, Clayton P, Rahman S, Reilly MM, Ouvrier RA, Christodoulou J, Züchner S, Muntoni F, Houlden H. Brain. 2014 Jan;137(Pt 1):44-56. doi: 10.1093/brain/awt315. Epub 2013 Nov 19.

Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Am J Hum Genet. 2014 Nov 6;95(5):590-601. doi: 10.1016/j.ajhg.2014.10.002. Epub 2014 Oct 30.

A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. Sumner CJ, d'Ydewalle C, Wooley J, Fawcett KA, Hernandez D, Gardiner AR, Kalmar B, Baloh RH, Gonzalez M, Züchner S, Stanescu HC, Kleta R, Mankodi A, Cornblath DR, Boylan KB, Reilly MM, Greensmith L, Singleton AB, Harms MB, Rossor AM, Houlden H. Am J Hum Genet. 2013 Nov 7;93(5):976-83. doi: 10.1016/j.ajhg.2013.10.006. Epub 2013 Oct 24.

A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo. Vester A, Velez-Ruiz G, McLaughlin HM; NISC Comparative Sequencing Program, Lupski JR, Talbot K, Vance JM, Züchner S, Roda RH, Fischbeck KH, Biesecker LG, Nicholson G, Beg AA, Antonellis A. Hum Mutat. 2013 Jan;34(1):191-9. doi: 10.1002/humu.22210. Epub 2012 Oct 11.

A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. Kennerson ML, Yiu EM, Chuang DT, Kidambi A, Tso SC, Ly C, Chaudhry R, Drew AP, Rance G, Delatycki MB, Züchner S, Ryan MM, Nicholson GA. Hum Mol Genet. 2013 Apr 1;22(7):1404-16. doi: 10.1093/hmg/dds557. Epub 2013 Jan 7.

A novel prion disease associated with diarrhea and autonomic neuropathy. Mead S, Gandhi S, Beck J, Caine D, Gallujipali D, Carswell C, Hyare H, Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz T, Sandberg MK, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S, Warren JD, Wadsworth JDF, Wood NW, Holton JL, Collinge J. N Engl J Med. 2013 Nov 14;369(20):1904-14. doi: 10.1056/NEJMoa1214747.

A review of genetic counseling for Charcot Marie Tooth disease (CMT). Siskind CE, Panchal S, Smith CO, et al. J Genet Couns. Aug 2013;22(4):422-436. PMID: 23604902.

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Boukhris A, Schule R, Loureiro JL, et al. Am J Hum Genet. Jul 11 2013;93(1):118-123. PMID: 23746551, PMCID: PMC3710753.

Anterior tibialis CMAP amplitude correlations with impairment in CMT1A. Komyathy K, Neal S, Feely S, Miller LJ, Lewis RA, Trigge G, Siskind CE, Shy ME, Ramchandren S. Muscle Nerve. 2013 Apr;47(4):493-6. doi: 10.1002/mus.23614. Epub 2013 Mar 3.

Asymmetric sensory ganglionopathy: a case series. Marquez-Infante C, Murphy SM, Mathew L, Alsanousi A, Lunn MP, Brandner S, Yousry TA, Blake J, Reilly MM. Muscle Nerve. 2013 Jul;48(1):145-50. doi: 10.1002/mus.23772. Epub 2013 Jun 6.

COX10 mutations resulting in complex multisystem mitochondrial disease that remains stable into adulthood. Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, Hargreaves I, Land JM, Nanji T, Polke JM, Woodward CE, Sweeney MG, Solanki S, Foley AR, Hurles ME, Stalker J, Blake J, Holton JL, Phadke R, Muntoni F, Reilly MM, Hanna MG; UK10K Consortium. JAMA Neurol. 2013 Dec;70(12):1556-61. doi: 10.1001/jamaneurol.2013.3242.

Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Rossor AM, Polke JM, Houlden H, Reilly MM. Nat Rev Neurol. 2013 Oct;9(10):562-71. doi: 10.1038/nrneurol.2013.179. Epub 2013 Sep 10.

DNA testing in hereditary neuropathies. Murphy SM, Laurá M, Reilly MM. Handb Clin Neurol. 2013;115:213-32. doi: 10.1016/B978-0-444-52902-2.00012-6.

Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age. Eschbach J, Sinniger J, Bouitbir J, Fergani A, Schlagowski AI, Zoll J, Geny B, René F, Larmet Y, Marion V, Baloh RH, Harms MB, Shy ME, Messadeq N, Weydt P, Loeffler JP, Ludolph AC, Dupuis L. Neurobiol Dis. 2013 Oct;58:220-30. doi: 10.1016/j.nbd.2013.05.015. Epub 2013 Jun 4.

Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2. Gonzalez M, McLaughlin H, Houlden H, Guo M, Yo-Tsen L, Hadjivassilious M, Speziani F, Yang XL, Antonellis A, Reilly MM, Züchner S; Inherited Neuropathy Consortium. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):1247-9. doi: 10.1136/jnnp-2013-305049. Epub 2013 Jun 1.

Genetic testing practices for CMT1A. Tousignant R, Trepanier A, Shy ME, Siskind CE. Muscle Nerve. Aug 20 2013. PMID: 23963961.

Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12. Landoure G, Zhu PP, Lourenco CM, et al. Hum Mutat. Oct 2013;34(10):1357-1360. PMID: 23857908, PMCID: PMC3819934.

Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2. Murphy SM, Ernst D, Wei Y, Laurà M, Liu YT, Polke J, Blake J, Winer J, Houlden H, Hornemann T, Reilly MM. Neurology. 2013 Jun 4;80(23):2106-11. doi: 10.1212/WNL.0b013e318295d789. Epub 2013 May 8.

High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial. Lewis RA, McDermott MP, Herrmann DN, Hoke A, Clawson LL, Siskind C, Feely SM, Miller LJ, Barohn RJ, Smith P, Luebbe E, Wu X, Shy ME; Muscle Study Group. JAMA Neurol. 2013 Aug;70(8):981-7. doi: 10.1001/jamaneurol.2013.3178.

Impact of nocturnal calf cramping on quality of sleep and health- related quality of life. Hawke F, Chuter V, Burns J. Qual Life Res. Aug 2013;22(6):1281-1286. PMID: 23011494.

Inherited neuropathies: an update. Sagnelli A, Piscosquito G, Pareyson D. J Neurol. Oct 2013;260(10):2684-2690. PMID: 24061768.

Inherited neuropathies: clinical overview and update. Klein CJ, Duan X, Shy ME. Muscle Nerve. 2013 Oct;48(4):604-22. doi: 10.1002/mus.23775. Epub 2013 Jun 26.

Inherited peripheral neuropathies. Saporta MA, Shy ME. Neurol Clin. 2013 May;31(2):597-619. doi: 10.1016/j.ncl.2013.01.009. Epub 2013 Mar 5.

Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia. Martin E, Schule R, Smets K, et al. Am J Hum Genet. Feb 7 2013;92(2):238- 244. PMID: 23332916, PMCID: PMC3567271.

Measuring Ankle Instability in Pediatric Charcot- Marie-Tooth Disease. Mandarakas M, Hiller CE, Rose KJ, Burns J. J Child Neurol. Nov 2013;28(11):1456-1462. PMID: 23696628.

Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. Oates EC, Rossor AM, Hafezparast M, Gonzalez M, Speziani F, MacArthur DG, Lek M, Cottenie E, Scoto M, Foley AR, Hurles M, Houlden H, Greensmith L, Auer-Grumbach M, Pieber TR, Strom TM, Schule R, Herrmann DN, Sowden JE, Acsadi G, Menezes MP, Clarke NF, Züchner S; UK10K, Muntoni F, North KN, Reilly MM. Am J Hum Genet. 2013 Jun 6;92(6):965-73. doi: 10.1016/j.ajhg.2013.04.018. Epub 2013 May 9.

Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54). Gonzalez M, Nampoothiri S, Kornblum C, et al. Eur J Hum Genet. Nov 2013;21(11):1214-1218. PMID: 23486545, PMCID: PMC3798837.

Natural History Baseline Phenotype and Genotype of Hereditary Motor Sensory Peripheral Neuropathies Caused by Mutation in the Myelin Protein Zero. Sanmaneechai O, Feely S, Finkel R, et al. Paper presented at: 2013 Peripheral Nerve Society Biennial Meeting; June 29–July 3, 2013; Saint-Malo, France.

Patient identification of the symptomatic impact of charcot-marie-tooth disease type 1A. Johnson NE, Heatwole CR, Ferguson M, Sowden JE, Jeanat S, Herrmann DN. J Clin Neuromuscul Dis. 2013 Sep;15(1):19-23. doi: 10.1097/CND.0b013e31829e22e3.

Peripheral neuropathy in mitochondrial disorders. Pareyson D, Piscosquito G, Moroni I, Salsano E, Zeviani M. Lancet Neurol. Oct 2013;12(10):1011-1024. PMID: 24050734.

Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy. Cottenie E, Menezes MP, Rossor AM, Morrow JM, Yousry TA, Dick DJ, Anderson JR, Jaunmuktane Z, Brandner S, Blake JC, Houlden H, Reilly MM. Neuromuscul Disord. 2013 May;23(5):399-403. doi: 10.1016/j.nmd.2013.01.010. Epub 2013 Mar 13.

The ARSACS phenotype can include supranuclear gaze palsy and skin lipofuscin deposits. Stevens JC, Murphy SM, Davagnanam I, Phadke R, Anderson G, Nethisinghe S, Bremner F, Giunti P, Reilly MM. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):114-6. doi: 10.1136/jnnp-2012-303634. Epub 2012 Nov 3.

The Rare Diseases Clinical Research Network Contact Registry for the Inherited Neuropathies Consortium. Hall CA, Bacon CJ, Shy ME, Inherited Neuropathies Consortium, Rare Diseases Clinical Research Network Data Management and Coordinating Center. Paper presented at: Charcot-Marie-Tooth Association, 5th International CMT Consortium Meeting; Jun. 25-27, 2013; Antwerp, Belgium.

Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children, adolescents, and young adults with Charcot-Marie-Tooth disease. Burns J, Menezes M, Finkel RS, Estilow T, Moroni I, Pagliano E, Laurá M, Muntoni F, Herrmann DN, Eichinger K, Shy R, Pareyson D, Reilly MM, Shy ME. J Peripher Nerv Syst. 2013 Jun;18(2):177-80. doi: 10.1111/jns5.12024.

A novel p.Gln175X [corrected] premature stop mutation in the C-terminal end of HSP27 is a cause of CMT2. Rossor AM, Davidson GL, Blake J, Polke JM, Murphy SM, Houlden H, Innes A, Kalmar B, Greensmith L, Reilly MM. J Peripher Nerv Syst. 2012 Jun;17(2):201-5. doi: 10.1111/j.1529-8027.2012.00400.x.

A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N). McLaughlin HM, Sakaguchi R, Giblin W; NISC Comparative Sequencing Program, Wilson TE, Biesecker L, Lupski JR, Talbot K, Vance JM, Züchner S, Lee YC, Kennerson M, Hou YM, Nicholson G, Antonellis A. Hum Mutat. 2012 Jan;33(1):244-53. doi: 10.1002/humu.21635. Epub 2011 Nov 9.

Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. Tesson C, Nawara M, Salih MA, et al. Am J Hum Genet. Dec 7 2012;91(6):1051-1064. PMID: 23176821, PMCID: PMC3516610.

Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes. Murphy SM, Khan U, Alifrangis C, Hazell S, Hrouda D, Blake J, Ball J, Gabriel C, Markarian P, Rees J, Karim A, Seckl MJ, Lunn MP, Reilly MM. J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):232-3. doi: 10.1136/jnnp.2010.223271. Epub 2011 Jan 4.

BAG3 mutations: another cause of giant axonal neuropathy. Jaffer F, Murphy SM, Scoto M, Healy E, Rossor AM, Brandner S, Phadke R, Selcen D, Jungbluth H, Muntoni F, Reilly MM. J Peripher Nerv Syst. 2012 Jun;17(2):210-6. doi: 10.1111/j.1529-8027.2012.00409.x.

Charcot-Marie-Tooth disease and related genetic neuropathies. Patzko A, Shy ME. Continuum (Minneapolis, Minn.). Feb 2012;18(1):39-59. PMID: 22810069.

Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL, Rossor AM, Polke JM, Castleman V, Manji H, Lunn MP, Bull K, Ramdharry G, Davis M, Blake JC, Houlden H, Reilly MM. J Neurol Neurosurg Psychiatry. 2012 Jul;83(7):706-10. doi: 10.1136/jnnp-2012-302451. Epub 2012 May 10.

Comprehensive analysis of the TRPV4 gene in a large series of inherited neuropathies and controls. Fawcett KA, Murphy SM, Polke JM, Wray S, Burchell VS, Manji H, Quinlivan RM, Zdebik AA, Reilly MM, Houlden H. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1204-9. doi: 10.1136/jnnp-2012-303055. Epub 2012 Jul 31.

Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice. Patzkó A, Bai Y, Saporta MA, Katona I, Wu X, Vizzuso D, Feltri ML, Wang S, Dillon LM, Kamholz J, Kirschner D, Sarkar FH, Wrabetz L, Shy ME. Brain. 2012 Dec;135(Pt 12):3551-66. doi: 10.1093/brain/aws299.

Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. Norton N, Robertson PD, Rieder MJ, Züchner S, Rampersaud E, Martin E, Li D, Nickerson DA, Hershberger RE; National Heart, Lung and Blood Institute GO Exome Sequencing Project. Circ Cardiovasc Genet. 2012 Apr 1;5(2):167-74. doi: 10.1161/CIRCGENETICS.111.961805. Epub 2012 Feb 15.

Exploring the experience of fatigue in people with Charcot-Marie-Tooth disease. Ramdharry GM, Thornhill A, Mein G, Reilly MM, Marsden JF. Neuromuscul Disord. Dec 2012;22 Suppl 3:S208- 213. PMID: 23182641.

Flexor digitorum superficialis opposition tendon transfer improves hand function in children with Charcot-Marie-Tooth disease: case series. Estilow T, Kozin SH, Glanzman AM, Burns J, Finkel RS. Neuromuscul Disord. 2012 Dec;22(12):1090-5. doi: 10.1016/j.nmd.2012.07.011. Epub 2012 Sep 1.

Foot drop splints improve proximal as well as distal leg control during gait in Charcot-Marie-Tooth disease. Ramdharry GM, Day BL, Reilly MM, Marsden JF. Muscle Nerve. Oct 2012;46(4):512- 519. PMID: 22987691.

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. Davidson G, Murphy S, Polke J, Laura M, Salih M, Muntoni F, Blake J, Brandner S, Davies N, Horvath R, Price S, Donaghy M, Roberts M, Foulds N, Ramdharry G, Soler D, Lunn M, Manji H, Davis M, Houlden H, Reilly M. J Neurol. 2012 Aug;259(8):1673-85. doi: 10.1007/s00415-011-6397-y.

Gap junctions in inherited human disorders of the central nervous system. Abrams CK, Scherer SS. Biochim Biophys Acta. Aug 2012;1818(8):2030-2047. PMID: 21871435, PMCID: PMC3771870.

Genetic Mutations Affecting Myelin Formation. Scherer SS, Feltri ML, Wrabetz L. In: Kettenmann H, Ransom BR, eds. Neuroglia. New York, NY: Oxford University Press; 2012:798-808.

Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease. Pitceathly RD, Murphy SM, Cottenie E, Chalasani A, Sweeney MG, Woodward C, Mudanohwo EE, Hargreaves I, Heales S, Land J, Holton JL, Houlden H, Blake J, Champion M, Flinter F, Robb SA, Page R, Rose M, Palace J, Crowe C, Longman C, Lunn MP, Rahman S, Reilly MM, Hanna MG. Neurology. 2012 Sep 11;79(11):1145-54. doi: 10.1212/WNL.0b013e3182698d8d. Epub 2012 Aug 29.

Hand weakness in Charcot-Marie-Tooth disease 1X. Arthur-Farraj PJ, Murphy SM, Laura M, Lunn MP, Manji H, Blake J, Ramdharry G, Fox Z, Reilly MM. Neuromuscul Disord. 2012 Jul;22(7):622-6. doi: 10.1016/j.nmd.2012.02.008. Epub 2012 Mar 28.

Hereditary amyloid neuropathy. Murphy SM, Reilly M. Autonomic Failure: a textbook of clinical disorders of the autonomic nervous system. New York: Oxford University Press; 2012.

How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease?. Kleopa KA, Abrams CK, Scherer SS. Brain Res. 2012 Dec 3;1487:198-205. doi: 10.1016/j.brainres.2012.03.068. Epub 2012 Jul 6.

Isolated motor conduction block associated with infliximab. Michell AW, Gaitatzis A, Burge J, Reilly MM, Kapoor R, Koltzenburg M. J Neurol. 2012 Aug;259(8):1758-60. doi: 10.1007/s00415-012-6452-3. Epub 2012 Feb 18.

Knee bobbing in Charcot-Marie-Tooth disease. Rossor AM, Murphy S, Reilly MM. Pract Neurol. 2012 Jun;12(3):182-3. doi: 10.1136/practneurol-2011-000167.

Lessons from London. Shy ME. J Neurol Neurosurg Psychiatry. 2012 Aug;83(8):767-8. doi: 10.1136/jnnp-2012-302858. Epub 2012 Jun 13.

Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Zimoń M, Baets J, Almeida-Souza L, De Vriendt E, Nikodinovic J, Parman Y, Battaloğlu E, Matur Z, Guergueltcheva V, Tournev I, Auer-Grumbach M, De Rijk P, Petersen BS, Müller T, Fransen E, Van Damme P, Löscher WN, Barišić N, Mitrovic Z, Previtali SC, Topaloğlu H, Bernert G, Beleza-Meireles A, Todorovic S, Savic-Pavicevic D, Ishpekova B, Lechner S, Peeters K, Ooms T, Hahn AF, Züchner S, Timmerman V, Van Dijck P, Rasic VM, Janecke AR, De Jonghe P, Jordanova A. Nat Genet. 2012 Oct;44(10):1080-3. doi: 10.1038/ng.2406. Epub 2012 Sep 9.

MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot-Marie-Tooth disease type 1B. Saporta MA, Shy BR, Patzko A, Bai Y, Pennuto M, Ferri C, Tinelli E, Saveri P, Kirschner D, Crowther M, Southwood C, Wu X, Gow A, Feltri ML, Wrabetz L, Shy ME. Brain. 2012 Jul;135(Pt 7):2032-47. doi: 10.1093/brain/aws140. Epub 2012 Jun 10.

Mutation in FAM134B causing severe hereditary sensory neuropathy. Murphy SM, Davidson GL, Brandner S, Houlden H, Reilly MM. J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):119-20. doi: 10.1136/jnnp.2010.228965. Epub 2010 Nov 28.

Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. Montenegro G, Rebelo AP, Connell J, et al. J Clin Invest. Feb 1 2012;122(2):538-544. PMID: 22232211, PMCID: PMC3266795.

Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. Harms MB, Ori-McKenney KM, Scoto M, Tuck EP, Bell S, Ma D, Masi S, Allred P, Al-Lozi M, Reilly MM, Miller LJ, Jani-Acsadi A, Pestronk A, Shy ME, Muntoni F, Vallee RB, Baloh RH. Neurology. 2012 May 29;78(22):1714-20. doi: 10.1212/WNL.0b013e3182556c05. Epub 2012 Mar 28.

Peripheral Neuropathies. Shy M. Goldman's Cecil Medicine: Expert Consult Premium Edition. Philadelphia, PA: Elsevier; 2012:2396-2409.

Phenotypic presentation of the Ser63Del MPZ mutation. Miller LJ, Patzko A, Lewis RA, Shy ME. J Peripher Nerv Syst. 2012 Jun;17(2):197-200. doi: 10.1111/j.1529-8027.2012.00398.x.

Rituximab responsive multiple radiculopathies and cranial nerve palsies in association with chronic lymphocytic leukaemia. Morrow JM, D'Sa S, Page RA, Hilali MA, Lunn MP, Reilly MM. J Neurol. Mar 2012;259(3):571-573. PMID: 21887515.

Severe Dejerine-Sottas disease with respiratory failure and dysmorphic features in association with a PMP22 point mutation and a 3q23 microdeletion. Voermans NC, Kleefstra T, Gabreels-Festen AA, et al. J Peripher. Nerv. Syst. Jun 2012;17(2):223-225. PMID: 22734911.

Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies. Sinclair CD, Morrow JM, Miranda MA, Davagnanam I, Cowley PC, Mehta H, Hanna MG, Koltzenburg M, Yousry TA, Reilly MM, Thornton JS. J Neurol Neurosurg Psychiatry. Jan 2012;83(1):29-32. PMID: 21613652.

Symmetry of foot alignment and ankle flexibility in paediatric Charcot-Marie-Tooth disease. Burns J, Ouvrier R, Estilow T, Shy R, Laurá M, Eichinger K, Muntoni F, Reilly MM, Pareyson D, Acsadi G, Shy ME, Finkel RS. Clin Biomech (Bristol, Avon). 2012 Aug;27(7):744-7. doi: 10.1016/j.clinbiomech.2012.02.006. Epub 2012 Mar 16.

The distal hereditary motor neuropathies. Rossor AM, Kalmar B, Greensmith L, Reilly MM. J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):6-14. doi: 10.1136/jnnp-2011-300952. Epub 2011 Oct 25.

The p150(Glued) CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Lloyd TE, Machamer J, O'Hara K, et al. Neuron. Apr 26 2012;74(2):344-360. PMID: 22542187, PMCID: PMC3353876.

Unintended effects of orphan product designation for rare neurological diseases. Murphy SM, Puwanant A, Griggs RC; Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and Inherited Neuropathies Consortium (INC) Consortia of the Rare Disease Clinical Research Network. Ann Neurol. 2012 Oct;72(4):481-90. doi: 10.1002/ana.23672.

Validation of the Charcot-Marie-Tooth disease pediatric scale as an outcome measure of disability. Burns J, Ouvrier R, Estilow T, Shy R, Laurá M, Pallant JF, Lek M, Muntoni F, Reilly MM, Pareyson D, Acsadi G, Shy ME, Finkel RS. Ann Neurol. 2012 May;71(5):642-52. doi: 10.1002/ana.23572.

X inactivation in females with X-linked Charcot-Marie-Tooth disease. Murphy SM, Ovens R, Polke J, Siskind CE, Laurà M, Bull K, Ramdharry G, Houlden H, Murphy RP, Shy ME, Reilly MM. Neuromuscul Disord. 2012 Jul;22(7):617-21. doi: 10.1016/j.nmd.2012.02.009. Epub 2012 Apr 6.

X-linked Charcot-Marie-Tooth disease. Scherer SS, Kleopa KA. J Peripher Nerv Syst. 2012 Dec;17 Suppl 3(0 3):9-13. doi: 10.1111/j.1529-8027.2012.00424.x.

dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Osterloh JM, Yang J, Rooney TM, Fox AN, Adalbert R, Powell EH, Sheehan AE, Avery MA, Hackett R, Logan MA, MacDonald JM, Ziegenfuss JS, Milde S, Hou YJ, Nathan C, Ding A, Brown RH Jr, Conforti L, Coleman M, Tessier-Lavigne M, Züchner S, Freeman MR. Science. 2012 Jul 27;337(6093):481-4. doi: 10.1126/science.1223899. Epub 2012 Jun 7.

A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease. Murphy SM, Polke J, Manji H, Blake J, Reiniger L, Sweeney M, Houlden H, Brandner S, Reilly MM. J Peripher Nerv Syst. 2011 Mar;16(1):65-70. doi: 10.1111/j.1529-8027.2011.00321.x.

A painful right leg. Smith LJ, Murphy SM, Holmes P, Reilly MM, Reiniger L, Thom M, Lunn MP. BMJ. 2011;342:d1009. PMID: 21411806.

Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Pareyson D, Reilly MM, Schenone A, et al. Lancet Neurol. Apr 2011;10(4):320-328. PMID: 21393063, PMCID: PMC3154498.

Axonal Charcot-Marie-Tooth disease. Shy ME, Patzkó A. Curr Opin Neurol. 2011 Oct;24(5):475-83. doi: 10.1097/WCO.0b013e32834aa331.

CMT2A: the name doesn't tell the whole story. Scherer SS. Neurology. May 17 2011;76(20):1686-1687. PMID: 21508332.

Charcot-Marie-Tooth disease. Reilly MM, Murphy SM, Laurá M. J Peripher Nerv Syst. 2011 Mar;16(1):1-14. doi: 10.1111/j.1529-8027.2011.00324.x.

Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Saporta AS, Sottile SL, Miller LJ, Feely SM, Siskind CE, Shy ME. Ann Neurol. 2011 Jan;69(1):22-33. doi: 10.1002/ana.22166.

Conduction block and tonic pupils in Charcot-Marie-Tooth disease caused by a myelin protein zero p.Ile112Thr mutation. Murphy SM, Laurá M, Blake J, Polke J, Bremner F, Reilly MM. Neuromuscul Disord. 2011 Mar;21(3):223-6. doi: 10.1016/j.nmd.2010.12.010. Epub 2011 Jan 21.

Distinct pathogenic processes between Fig4-deficient motor and sensory neurons. Katona I, Zhang X, Bai Y, et al. Eur J Neurosci. Apr 2011;33(8):1401-1410. PMID: 21410794.

Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Montenegro G, Powell E, Huang J, Speziani F, Edwards YJ, Beecham G, Hulme W, Siskind C, Vance J, Shy M, Züchner S. Ann Neurol. 2011 Mar;69(3):464-70. doi: 10.1002/ana.22235. Epub 2011 Jan 20.

Genetics of neuropathies. Siskind CE, Shy ME. Semin Neurol. Nov 2011;31(5):494-505. PMID: 22266887.

In vivo confocal microscopy of Meissner corpuscles as a novel sensory measure in CMT1A. Almodovar JL, Ferguson M, McDermott MP, Lewis RA, Shy ME, Herrmann DN. J Peripher Nerv Syst. 2011 Sep;16(3):169-74. doi: 10.1111/j.1529-8027.2011.00342.x.

Induced pluripotent stem cells in the study of neurological diseases. Saporta MA, Grskovic M, Dimos JT. Stem cell research & therapy. 2011;2(5):37. PMID: 21936964, PMCID: PMC3308034.

Inherited peripheral neuropathies. Shy ME. Continuum (Minneapolis, Minn.). Apr 2011;17(2 Neurogenetics):294-315. PMID: 22810821.

MFN2 mutations cause severe phenotypes in most patients with CMT2A. Feely SM, Laura M, Siskind CE, Sottile S, Davis M, Gibbons VS, Reilly MM, Shy ME. Neurology. 2011 May 17;76(20):1690-6. doi: 10.1212/WNL.0b013e31821a441e. Epub 2011 Apr 20.

Microtubules, axonal transport, and neuropathy. Holzbaur EL, Scherer SS. N Engl J Med. 2011 Dec 15;365(24):2330-2. doi: 10.1056/NEJMcibr1112481.

Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2. McCorquodale DS, 3rd, Montenegro G, Peguero A, et al. J Neurol. Jul 2011;258(7):1234-1239. PMID: 21258814, PMCID: PMC3125445.

Neuropathy in a human without the PMP22 gene. Saporta MA, Katona I, Zhang X, Roper HP, McClelland L, Macdonald F, Brueton L, Blake J, Suter U, Reilly MM, Shy ME, Li J. Arch Neurol. Jun 2011;68(6):814-821. PMID: 21670407, PMCID: PMC3711535.

Phenotype expression in women with CMT1X. Siskind CE, Murphy SM, Ovens R, Polke J, Reilly MM, Shy ME. J Peripher Nerv Syst. 2011 Jun;16(2):102-7. doi: 10.1111/j.1529-8027.2011.00332.x.

Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations. Polke JM, Laura M, Pareyson D, et al. Neurology. Jul 12 2011;77(2):168-173. PMID: 21715711, PMCID: PMC3140074.

Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. Murphy SM, Herrmann DN, McDermott MP, Scherer SS, Shy ME, Reilly MM, Pareyson D. J Peripher Nerv Syst. 2011 Sep;16(3):191-8. doi: 10.1111/j.1529-8027.2011.00350.x.

Strategy for genetic testing in Charcot-Marie-disease. Miller LJ, Saporta AS, Sottile SL, Siskind CE, Feely SM, Shy ME. Acta Myol. 2011 Oct;30(2):109-16.

The death panel for Charcot-Marie-Tooth panels. Amato AA, Reilly MM. Ann Neurol. Jan 2011;69(1):1-4. PMID: 21280068.

The debut of a rational treatment for an inherited neuropathy. Scherer SS. J Clin Invest. Dec 2011;121(12):4624-4627. PMID: 22045569, PMCID: PMC3226011.

Update on Charcot-Marie-Tooth disease. Patzkó A, Shy ME. Curr Neurol Neurosci Rep. 2011 Feb;11(1):78-88. doi: 10.1007/s11910-010-0158-7.

Variable phenotypes are associated with PMP22 missense mutations. Russo M, Laura M, Polke JM, et al. Neuromuscul Disord. Feb 2011;21(2):106-114. PMID: 21194947.

Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa. Züchner S, Dallman J, Wen R, Beecham G, Naj A, Farooq A, Kohli MA, Whitehead PL, Hulme W, Konidari I, Edwards YJ, Cai G, Peter I, Seo D, Buxbaum JD, Haines JL, Blanton S, Young J, Alfonso E, Vance JM, Lam BL, Peričak-Vance MA. Am J Hum Genet. 2011 Feb 11;88(2):201-6. doi: 10.1016/j.ajhg.2011.01.001. Epub 2011 Feb 3.

c-Jun expression in human neuropathies: a pilot study. Hutton EJ, Carty L, Laurá M, Houlden H, Lunn MP, Brandner S, Mirsky R, Jessen K, Reilly MM. J Peripher Nerv Syst. 2011 Dec;16(4):295-303. doi: 10.1111/j.1529-8027.2011.00360.x.

168th ENMC International Workshop: outcome measures and clinical trials in Charcot-Marie-Tooth disease (CMT). Reilly MM, Shy ME, Muntoni F, Pareyson D. Neuromuscul Disord. Dec 2010;20(12):839-846. PMID: 20850975.

Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease. Huang J, Wu X, Montenegro G, et al. J Neurol. May 2010;257(5):735-741. PMID: 19949810, PMCID: PMC2865568.

Determinants of reduced health-related quality of life in pediatric inherited neuropathies. Burns J, Ramchandren S, Ryan MM, Shy M, Ouvrier RA. Neurology. 2010 Aug 24;75(8):726-31. doi: 10.1212/WNL.0b013e3181eee496.

Genes and Inherited Neuropathies. Scherer SS. Companion to Peripheral Neuropathy. Philadelphia, PA: Saunders Elsevier; 2010:335-342.

Quality of life in children with Charcot-Marie-Tooth disease. Burns J, Ryan MM, Ouvrier RA. J Child Neurol. Mar 2010;25(3):343-347. PMID: 19713553.

SeqEM: an adaptive genotype-calling approach for next-generation sequencing studies. Martin ER, Kinnamon DD, Schmidt MA, Powell EH, Zuchner S, Morris RW. Bioinformatics. 2010 Nov 15;26(22):2803-10. doi: 10.1093/bioinformatics/btq526. Epub 2010 Sep 21.

Ascorbic acid for treatment of CMT1A: the jury is still out. Shy M. Lancet Neurol. Jun 2009;8(6):505-507. PMID: 19427270.

Diagnosis and new treatments in genetic neuropathies. Reilly MM, Shy ME. Reilly MM, Shy ME. Diagnosis and new treatments in genetic neuropathies. J Neurol Neurosurg Psychiatry. Dec 2009;80(12):1304-1314. PMID: 19917815.

Exome sequencing of a multigenerational human pedigree. Hedges DJ, Burges D, Powell E, Almonte C, Huang J, Young S, Boese B, Schmidt M, Pericak-Vance MA, Martin E, Zhang X, Harkins TT, Züchner S. PLoS One. 2009 Dec 14;4(12):e8232. doi: 10.1371/journal.pone.0008232.

Hip flexor fatigue limits walking in Charcot-Marie-Tooth disease. Ramdharry GM, Day BL, Reilly MM, Marsden JF. Muscle Nerve. 2009 Jul;40(1):103-11. doi: 10.1002/mus.21264.

PMP22 expression in dermal nerve myelin from patients with CMT1A. Katona I, Wu X, Feely SM, et al. Brain. Jul 2009;132(Pt 7):1734-1740. PMID: 19447823, PMCID: PMC2724915.

Persistent CNS dysfunction in a boy with CMT1X. Siskind C, Feely SM, Bernes S, Shy ME, Garbern JY. J Neurol Sci. Apr 15 2009;279(1-2):109-113. PMID: 19193385.

Quality of life in children with CMT type 1A. Ramchandren S, Shy ME, Finkel RS. Lancet Neurol. Oct 2009;8(10):880-881; author reply 881. PMID: 19747650.

The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy. Houlden H, Laura M, Ginsberg L, et al. Neuromuscul Disord. Apr 2009;19(4):264-269. PMID: 19272779.

Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K. Science. Aug 29 2008;321(5893):1218-1221. PMID: 18669821.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN). Brima T, Freedman EG, Prinsloo KD, Augustine EF, Adams HR, Wang KH, Mink JW, Shaw LH, Mantel EP, Foxe JJ. J Neurodev Disord. 2024 Jan 6;16(1):3. doi: 10.1186/s11689-023-09515-8. PMID: 38183037; PMCID: PMC10770910.

CLN3 disease, also known as juvenile neuronal ceroid lipofuscinosis or Batten disease, is a type of lysosomal disorder that affects the nervous system beginning in childhood. Throughout adolescence and early adulthood, patients often experience progressive vision loss, motor dysfunction, and cognitive decline. This combination of symptoms can make it challenging to assess neurocognitive decline, highlighting the need for quantitative measures of brain function.

In this study, researchers assessed auditory sensory memory capabilities in individuals with CLN3 disease as a potential biomarker for neurocognitive decline. The team used a type of assessment called duration-evoked mismatch negativity (MMN)—which does not require participant engagement—to study early auditory processing, discrimination, and sensory memory in 21 individuals with CLN3 disease and 41 neurotypical controls.

Results reveal a decline in auditory sensory memory for duration as CLN3 disease progresses. Authors note that duration-evoked MMN may also serve as a sensitive measure of disease severity in other neurodevelopmental disorders.

Persistent bone and joint disease despite current treatments for mucopolysaccharidosis types I, II, and VI: Data from a 10-year prospective study. Miller BS, Fung EB, White KK, Lund TC, Harmatz P, Orchard PJ, Whitley CB, Polgreen LE. J Inherit Metab Dis. 2023 Feb 25. doi: 10.1002/jimd.12598. Epub ahead of print. PMID: 36840680.

Mucopolysaccharidosis (MPS) disorders are a group of nine rare, inherited, lysosomal storage disorders caused by genetic mutations which produce 11 dysfunctional enzymes that cannot break down glycosaminoglycans (complex sugar molecules with amino groups that are critical components of connective tissues). MPS disorders have many potential new therapies on the horizon. However, historic control data on disease progression and variability are needed to understand the long-term benefits and limitations of these treatments.

In this study, researchers conducted a 10-year prospective observational study of 55 children with multiple types of MPS. The team used several techniques, including annual measurements and mixed effects modeling, to systematically evaluate bone and joint disease over time.

Results show that despite current treatments, patients with MPS I, II, and VI still experience short stature, joint contractures, and elevation in average BMI. Authors note that data from this study could be used to expedite testing of therapies directed to bones and joints, as well as highlight the need for weight management in routine clinical care for patients with MPS.

Validation of the parent-proxy version of the pediatric Charcot-Marie-Tooth disease quality of life instrument for children aged 0-7 years. Wu TT, Finkel RS, Siskind CE, Feely SME, Burns J, Reilly MM, Muntoni F, Milev E, Estilow T, Shy ME, Ramchandren S; Childhood CMT Study Group of the Inherited Neuropathy Consortium. J Peripher Nerv Syst. 2023 Sep;28(3):382-389. doi: 10.1111/jns.12557. Epub 2023 May 18.

A novel unbiased method reveals progressive podocyte globotriaosylceramide accumulation and loss with age in females with Fabry disease. Silvestroni A, Sokolovskiy A, Tøndel C, Svarstad E, Obrisca B, Ismail G, Holida MD, Mauer M. Kidney Int. 2022 Jul;102(1):173-182. doi: 10.1016/j.kint.2022.03.023. Epub 2022 Apr 26. PMID: 35483528; PMCID: PMC9233139.

Fabry disease is a lysosomal storage disorder caused by an abnormal enzyme that cannot break down some of the glycosphingolipids (cell membrane components containing fats with sugar molecules attached). The increase in one of these glycosphingolipids, called globotriasylceramide (GL3), is the hallmark of the disease and associated with cellular injury. The Fabry disease gene is located on the X chromosome. In contrast to males, females have two X chromosomes in their cells, one of which is randomly inactivated. Although female patients can experience serious complications of Fabry disease, most studies focus on male patients in order to avoid confusion resulting from mosaicism caused by X chromosome inactivation. In this study, researchers developed a new, unbiased method for GL3 estimation in podocytes (kidney cells that wrap around capillaries in the kidney filters called glomeruli) independent of mosaicism in female patients with Fabry disease. Researchers used this method to make age-matched comparisons between female and male patients and controls. Results showed that GL3 accumulation in podocytes that carry the gene defect in female patients with Fabry disease increases with age—and to the same levels as podocytes in males, all of which carry this defect. This accumulation is also associated with podocyte loss and leaking protein in the urine, predictors of kidney failure. These studies indicate that Fabry-affected podocytes in female patients do not benefit from the circulating normal enzyme from their normal cells or from normal neighbor podocytes. Authors note that these novel findings help us better understand the mechanisms involved in Fabry disease complications and have important clinical implications.

Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease. Sahasrabudhe SA, Terluk MR, Rudser KD, Cloyd JC, Kartha RV. Int J Mol Sci. 2022 Aug 16;23(16):9189. doi: 10.3390/ijms23169189. PMID: 36012454; PMCID: PMC9409136.

Gaucher disease type 1 (GD1) is a rare lysosomal storage disorder in which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the body. Currently, there is a lack of reliable biomarkers for GD1, which could help predict treatment success or disease progression. In this study, researchers aimed to validate measures of oxidative stress and inflammation as biomarkers for GD1. For three months, the team investigated and compared variation in various blood-based oxidative stress and inflammation biomarkers in participants with GD1. Results show that specific biomarkers are consistently altered in GD1, regardless of therapy status. These findings highlight the need for additional therapies that can target and modulate these biomarkers. Authors note that this information can help guide the selection of candidate biomarkers for future intervention-based studies in patients with GD1.

Quantifying medical manifestations in Hurler syndrome with the infant physical symptom score: associations with long-term physical and adaptive outcomes. Ahmed A, Rudser K, King KE, Eisengart JB, Orchard PJ, Shapiro E, Whitley CB. Mol Genet Metab. 2022 May;136(1):22-27. doi: 10.1016/j.ymgme.2022.03.003. Epub 2022 Mar 10. PMID: 35304037.

Mucopolysaccharidosis (MPS) is a group of inherited conditions in which the body is unable to properly break down mucopolysaccharides (long chains of sugar molecules that are found throughout the body). As a result, these sugars build up in cells, blood, and connective tissue, leading to a variety of health problems. A physical symptom score (PSS) has been developed to characterize physical symptoms of MPS in older children. With the onset of newborn screening, there is an increased need to characterize these symptoms in infants and toddlers. In this study, researchers aimed to create a measure to quantify somatic (physical) burden in patients with MPS under 36 months of age. They established the Infant Physical Symptom Score (IPSS) using data from 39 patients with Hurler syndrome (MPS IH) enrolled in a Lysosomal Disease Network (LDN) study. To validate the new scale, researchers compared the IPSS with the PSS. Results show that the IPSS is a useful approach to quantifying the somatic disease burden of MPS IH patients under 36 months of age. Authors note that the IPSS may also provide a predictor of later outcomes, especially adaptive function.

A diagnostic confidence scheme for CLN3 disease. Masten MC, Corre C, Paciorkowski AR, Vierhile A, Adams HR, Vermilion J, Zimmerman GA, Augustine EF, Mink JW. J Inherit Metab Dis. 2021 Aug 28. doi: 10.1002/jimd.12429. Online ahead of print.

CLN3 disease is an inherited disorder that primarily affects the nervous system. After 4 to 6 years of normal development, children with this condition develop vision impairment, intellectual disability, movement problems, speech difficulties, and seizures, which worsen over time. Researchers seeking to improve diagnostic methods for CLN3 disease used genotype and phenotype data from an ongoing natural history study to develop a hierarchical diagnostic confidence scheme with three major classes: Definite, Probable, or Possible CLN3 disease. An additional level, CLN3 Disease PLUS, includes individuals with CLN3 disease plus an additional disorder that substantially affects the phenotype. They used the scheme to classify individuals and then performed a blinded reclassification to assess the reliability of this scheme. Test-retest reliability showed 96% agreement. Authors conclude that their diagnostic confidence scheme for CLN3 disease appears to be effective and has implications for clinical research in CLN3 and other rare genetic neurodegenerative disorders.

Automated Retinal Layer Segmentation in CLN2-Associated Disease: Commercially Available Software Characterizing a Progressive Maculopathy. Kovacs KD, Orlin A, Sondhi D, Kaminsky SM, D'Amico DJ, Crystal RG, Kiss S. Transl Vis Sci Technol. 2021 Jul 1;10(8):23. doi: 10.1167/tvst.10.8.23.

CLN2-associated disease is an inherited, fatal lysosomal storage disorder characterized by progressive brain and retinal deterioration. In this study, researchers evaluated the eyes of 14 patients using the automated segmentation software in optical coherence tomography scans to characterize inner and outer retinal degeneration. Their goal was to identify sensitive, quantitative biomarkers for assessing retinal degeneration in anticipation of future clinical trials. They identified a significant, progressive difference in the thickness of the outer nuclear layers (ONL) of the parafovea, a region in the retina, in patients from 39 to 45 months versus 46 to 52 months. They conclude that parafoveal ONL thickness is a sensitive, early age indicator of CLN2-associated retinal degeneration.

Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction. Li C, Desai AK, Gupta P, Dempsey K, Bhambhani V, Hopkin RJ, Ficicioglu C, Tanpaiboon P, Craigen WJ, Rosenberg AS, Kishnani PS. Genet Med. 2021 May;23(5):845-855. doi: 10.1038/s41436-020-01080-y. Epub 2021 Jan 25.

This study of 41 patients with cross-reactive immunological material (CRIM)-negative infantile Pompe disease (IPD) showed that early treatment with enzyme replacement therapy and prophylactic immune tolerance induction can transform the long-term CRIM-negative phenotype, which represents the most severe end of the Pompe disease spectrum.

Umbilical mesenchymal stem cell-derived extracellular vesicles as enzyme delivery vehicle to treat Morquio A fibroblasts. Flanagan M, Pathak I, Gan Q, Winter L, Emnet R, Akel S, Montaño AM. Stem Cell Res Ther. 2021 May 6;12(1):276. doi: 10.1186/s13287-021-02355-0.

A novel gene editing system to treat both Tay-Sachs and Sandhoff diseases. Ou L, Przybilla MJ, Tăbăran AF, Overn P, O'Sullivan MG, Jiang X, Sidhu R, Kell PJ, Ory DS, Whitley CB. Gene Ther. 2020 May;27(5):226-236. doi: 10.1038/s41434-019-0120-5. Epub 2020 Jan 2.

Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss. Najafian B, Tøndel C, Svarstad E, Gubler MC, Oliveira JP, Mauer M. J Am Soc Nephrol. 2020 Apr;31(4):865-875. doi: 10.1681/ASN.2019050497. Epub 2020 Mar 3.

Behavioral, social and school functioning in children with Pompe disease. Korlimarla A, Spiridigliozzi GA, Stefanescu M, Austin SL, Kishnani PS. Mol Genet Metab Rep. 2020 Aug 5;25:100635. doi: 10.1016/j.ymgmr.2020.100635. eCollection 2020 Dec.

Benefits of Prophylactic Short-Course Immune Tolerance Induction in Patients With Infantile Pompe Disease: Demonstration of Long-Term Safety and Efficacy in an Expanded Cohort. Desai AK, Baloh CH, Sleasman JW, Rosenberg AS, Kishnani PS. Front Immunol. 2020 Aug 6;11:1727. doi: 10.3389/fimmu.2020.01727. eCollection 2020.

Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I. Lund TC, Doherty TM, Eisengart JB, Freese RL, Rudser KD, Fung EB, Miller BS, White KK, Orchard PJ, Whitley CB, Polgreen LE. JIMD Rep. 2020 Dec 8;58(1):89-99. doi: 10.1002/jmd2.12190. eCollection 2021 Mar.

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation. Polgreen LE, Lund TC, Braunlin E, Tolar J, Miller BS, Fung E, Whitley CB, Eisengart JB, Northrop E, Rudser K, Miller WP, Orchard PJ. Pediatr Res. 2020 Jan;87(1):104-111. doi: 10.1038/s41390-019-0541-2. Epub 2019 Aug 21.

Evaluation of non-reducing end pathologic glycosaminoglycan detection method for monitoring therapeutic response to enzyme replacement therapy in human mucopolysaccharidosis I. Vera MU, Le SQ, Victoroff A, Passage MB, Brown JR, Crawford BE, Polgreen LE, Chen AH, Dickson PI. Mol Genet Metab. 2020 Feb;129(2):91-97. doi: 10.1016/j.ymgme.2019.09.001. Epub 2019 Sep 11.

GBA1 mutations: Prospects for exosomal biomarkers in α-synuclein pathologies. Johnson PH, Weinreb NJ, Cloyd JC, Tuite PJ, Kartha RV. Mol Genet Metab. 2020 Feb;129(2):35-46. doi: 10.1016/j.ymgme.2019.10.006. Epub 2019 Oct 23.

Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study. Chen AH, Harmatz P, Nestrasil I, Eisengart JB, King KE, Rudser K, Kaizer AM, Svatkova A, Wakumoto A, Le SQ, Madden J, Young S, Zhang H, Polgreen LE, Dickson PI. Mol Genet Metab. 2020 Feb;129(2):80-90. doi: 10.1016/j.ymgme.2019.11.007. Epub 2019 Nov 30.

Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy. Kartha RV, Joers J, Terluk MR, Travis A, Rudser K, Tuite PJ, Weinreb NJ, Jarnes JR, Cloyd JC, Öz G. J Inherit Metab Dis. 2020 May;43(3):564-573. doi: 10.1002/jimd.12182. Epub 2019 Dec 17.

Novel approaches to quantify CNS involvement in children with Pompe disease. Korlimarla A, Spiridigliozzi GA, Crisp K, Herbert M, Chen S, Malinzak M, Stefanescu M, Austin SL, Cope H, Zimmerman K, Jones H, Provenzale JM, Kishnani PS. Neurology. 2020 Aug 11;95(6):e718-e732. doi: 10.1212/WNL.0000000000009979. Epub 2020 Jun 9.

Overview of advances in educational and social supports for young persons with NCL disorders. Elmerskog B, Tøssebro AG, Atkinson R, Rokne S, Cole B, Ockelford A, Adams HR. Biochim Biophys Acta Mol Basis Dis. 2020 Sep 1;1866(9):165480. doi: 10.1016/j.bbadis.2019.05.016. Epub 2019 May 30.

Pulmonary outcome measures in long-term survivors of infantile Pompe disease on enzyme replacement therapy: A case series. ElMallah MK, Desai AK, Nading EB, DeArmey S, Kravitz RM, Kishnani PS. Pediatr Pulmonol. 2020 Mar;55(3):674-681. doi: 10.1002/ppul.24621. Epub 2020 Jan 3.

Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressing CLN2. Sondhi D, Kaminsky SM, Hackett NR, Pagovich OE, Rosenberg JB, De BP, Chen A, Van de Graaf B, Mezey JG, Mammen GW, Mancenido D, Xu F, Kosofsky B, Yohay K, Worgall S, Kaner RJ, Souwedaine M, Greenwald BM, Kaplitt M, Dyke JP, Ballon DJ, Heier LA, Kiss S, Crystal RG. Sci Transl Med. 2020 Dec 2;12(572):eabb5413. doi: 10.1126/scitranslmed.abb5413.

Symmetric Age Association of Retinal Degeneration in Patients with CLN2-Associated Batten Disease. Kovacs KD, Patel S, Orlin A, Kim K, Van Everen S, Conner T, Sondhi D, Kaminsky SM, D'Amico DJ, Crystal RG, Kiss S. Ophthalmol Retina. 2020 Jul;4(7):728-736. doi: 10.1016/j.oret.2020.01.011. Epub 2020 Jan 22.

The CLN3 Disease Staging System: A new tool for clinical research in Batten disease. Masten MC, Williams JD, Vermilion J, Adams HR, Vierhile A, Collins A, Marshall FJ, Augustine EF, Mink JW. Neurology. 2020 Jun 9;94(23):e2436-e2440. doi: 10.1212/WNL.0000000000009454. Epub 2020 Apr 16.

A longitudinal study of neurocognition and behavior in patients with Hurler-Scheie syndrome heterozygous for the L238Q mutation. Ahmed A, Ou L, Rudser K, Shapiro E, Eisengart JB, King K, Chen A, Dickson P, Whitley CB. Mol Genet Metab Rep. 2019 Jun 27;20:100484. doi: 10.1016/j.ymgmr.2019.100484. eCollection 2019 Sep.

An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease. Kazi ZB, Desai AK, Troxler RB, Kronn D, Packman S, Sabbadini M, Rizzo WB, Scherer K, Abdul-Rahman O, Tanpaiboon P, Nampoothiri S, Gupta N, Feigenbaum A, Niyazov DM, Sherry L, Segel R, McVie-Wylie A, Sung C, Joseph AM, Richards S, Kishnani PS. Genet Med. 2019 Apr;21(4):887-895. doi: 10.1038/s41436-018-0270-7. Epub 2018 Sep 14.

Early-onset of symptoms and clinical course of Pompe disease associated with the c.-32-13 T > G variant. Herbert M, Case LE, Rairikar M, Cope H, Bailey L, Austin SL, Kishnani PS. Mol Genet Metab. 2019 Feb;126(2):106-116. doi: 10.1016/j.ymgme.2018.08.009. Epub 2018 Aug 23.

Genotype-phenotype correlation of gangliosidosis mutations using in silico tools and homology modeling. Ou L, Kim S, Whitley CB, Jarnes-Utz JR. Mol Genet Metab Rep. 2019 Jul 17;20:100495. doi: 10.1016/j.ymgmr.2019.100495. eCollection 2019 Sep.

Intellectual functioning in alpha-mannosidosis. Cathey SS, Sarasua SM, Simensen R, Pietris K, Kimbrell G, Sillence D, Wilson C, Horowitz L. JIMD Rep. 2019 Sep 21;50(1):44-49. doi: 10.1002/jmd2.12073. eCollection 2019 Nov.

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes. Eisengart JB, Pierpont EI, Kaizer AM, Rudser KD, King KE, Pasquali M, Polgreen LE, Dickson PI, Le SQ, Miller WP, Tolar J, Orchard PJ, Lund TC. Genet Med. 2019 Nov;21(11):2552-2560. doi: 10.1038/s41436-019-0522-1. Epub 2019 Apr 25.

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. Pant DC, Dorboz I, Schluter A, Fourcade S, Launay N, Joya J, Aguilera-Albesa S, Yoldi ME, Casasnovas C, Willis MJ, Ruiz M, Ville D, Lesca G, Siquier-Pernet K, Desguerre I, Yan H, Wang J, Burmeister M, Brady L, Tarnopolsky M, Cornet C, Rubbini D, Terriente J, James KN, Musaev D, Zaki MS, Patterson MC, Lanpher BC, Klee EW, Pinto E Vairo F, Wohler E, Sobreira NLM, Cohen JS, Maroofian R, Galehdari H, Mazaheri N, Shariati G, Colleaux L, Rodriguez D, Gleeson JG, Pujades C, Fatemi A, Boespflug-Tanguy O, Pujol A. J Clin Invest. 2019 Mar 1;129(3):1240-1256. doi: 10.1172/JCI123959. Epub 2019 Feb 11.

Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease. Ou L, Przybilla MJ, Whitley CB. Mol Genet Metab. 2019 Feb;126(2):151-156. doi: 10.1016/j.ymgme.2018.09.005. Epub 2018 Sep 14.

Survey of quality of life, phenotypic expression, and response to treatment in Krabbe leukodystrophy. Langan TJ, Barczykowski A, Jalal K, Sherwood L, Allewelt H, Kurtzberg J, Carter RL. JIMD Rep. 2019 Apr 11;47(1):47-54. doi: 10.1002/jmd2.12033. eCollection 2019 May.

Aicardi goutières syndrome is associated with pulmonary hypertension. Adang LA, Frank DB, Gilani A, Takanohashi A, Ulrick N, Collins A, Cross Z, Galambos C, Helman G, Kanaan U, Keller S, Simon D, Sherbini O, Hanna BD, Vanderver AL. Mol Genet Metab. 2018 Dec;125(4):351-358. doi: 10.1016/j.ymgme.2018.09.004. Epub 2018 Sep 7.

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome. Shapiro EG, Whitley CB, Eisengart JB. Orphanet J Rare Dis. 2018 May 11;13(1):76. doi: 10.1186/s13023-018-0817-3.

Complex care of individuals with multiple sulfatase deficiency: Clinical cases and consensus statement. Ahrens-Nicklas R, Schlotawa L, Ballabio A, Brunetti-Pierri N, De Castro M, Dierks T, Eichler F, Ficicioglu C, Finglas A, Gaertner J, Kirmse B, Klepper J, Lee M, Olsen A, Parenti G, Vossough A, Vanderver A, Adang LA. Mol Genet Metab. 2018 Mar;123(3):337-346. doi: 10.1016/j.ymgme.2018.01.005. Epub 2018 Jan 31.

Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Nickel M, Simonati A, Jacoby D, Lezius S, Kilian D, Van de Graaf B, Pagovich OE, Kosofsky B, Yohay K, Downs M, Slasor P, Ajayi T, Crystal RG, Kohlschütter A, Sondhi D, Schulz A. Lancet Child Adolesc Health. 2018 Aug;2(8):582-590. doi: 10.1016/S2352-4642(18)30179-2. Epub 2018 Jul 2.

Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Nestrasil I, Ahmed A, Utz JM, Rudser K, Whitley CB, Jarnes-Utz JR. Mol Genet Metab. 2018 Feb;123(2):97-104. doi: 10.1016/j.ymgme.2017.12.432. Epub 2017 Dec 20.

Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation. Desai AK, Walters CK, Cope HL, Kazi ZB, DeArmey SM, Kishnani PS. Mol Genet Metab. 2018 Feb;123(2):92-96. doi: 10.1016/j.ymgme.2017.12.435. Epub 2017 Dec 23.

Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison. Eisengart JB, Rudser KD, Xue Y, Orchard P, Miller W, Lund T, Van der Ploeg A, Mercer J, Jones S, Mengel KE, Gökce S, Guffon N, Giugliani R, de Souza CFM, Shapiro EG, Whitley CB. Genet Med. 2018 Nov;20(11):1423-1429. doi: 10.1038/gim.2018.29. Epub 2018 Mar 8.

Low frequency of Fabry disease in patients with common heart disease. Schiffmann R, Swift C, McNeill N, Benjamin ER, Castelli JP, Barth J, Sweetman L, Wang X, Wu X. Genet Med. 2018 Jul;20(7):754-759. doi: 10.1038/gim.2017.175. Epub 2017 Oct 26.

Mutations in SZT2 result in early-onset epileptic encephalopathy and leukoencephalopathy. Pizzino A, Whitehead M, Sabet Rasekh P, Murphy J, Helman G, Bloom M, Evans SH, Murnick JG, Conry J, Taft RJ, Simons C, Vanderver A, Adang LA. Am J Med Genet A. 2018 Jun;176(6):1443-1448. doi: 10.1002/ajmg.a.38717. Epub 2018 Apr 25.

Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. McIntosh PT, Hobson-Webb LD, Kazi ZB, Prater SN, Banugaria SG, Austin S, Wang R, Enterline DS, Frush DP, Kishnani PS. Mol Genet Metab. 2018 Feb;123(2):85-91. doi: 10.1016/j.ymgme.2017.10.005. Epub 2017 Oct 13.

Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case series. Shapiro E, Ahmed A, Whitley C, Delaney K. Mol Genet Metab. 2018 Feb;123(2):123-126. doi: 10.1016/j.ymgme.2017.11.014. Epub 2017 Nov 28.

RTB lectin-mediated delivery of lysosomal α-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Ou L, Przybilla MJ, Koniar B, Whitley CB. Mol Genet Metab. 2018 Feb;123(2):105-111. doi: 10.1016/j.ymgme.2017.11.013. Epub 2017 Nov 28.

SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases. Ou L, Przybilla MJ, Whitley CB. Clin Genet. 2018 May;93(5):1008-1014. doi: 10.1111/cge.13226. Epub 2018 Mar 5.

Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease). Sindelar M, Dyke JP, Deeb RS, Sondhi D, Kaminsky SM, Kosofsky BE, Ballon DJ, Crystal RG, Gross SS. Sci Rep. 2018 Oct 15;8(1):15229. doi: 10.1038/s41598-018-33449-0.

Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance. Kim J, Sinha S, Solomon M, Perez-Herrero E, Hsu J, Tsinas Z, Muro S. Biomaterials. 2017 Dec;147:14-25. doi: 10.1016/j.biomaterials.2017.08.045. Epub 2017 Sep 6.

Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up. Spiridigliozzi GA, Keeling LA, Stefanescu M, Li C, Austin S, Kishnani PS. Mol Genet Metab. 2017 Jun;121(2):127-137. doi: 10.1016/j.ymgme.2017.04.014. Epub 2017 May 1.

Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report. Kim S, Whitley CB, Jarnes Utz JR. Mol Genet Metab. 2017 Sep;122(1-2):92-99. doi: 10.1016/j.ymgme.2017.06.001. Epub 2017 Jun 3.

Delayed Infusion Reactions to Enzyme Replacement Therapies. Karimian Z, Whitley CB, Rudser KD, Utz JRJ. JIMD Rep. 2017;34:63-70. doi: 10.1007/8904_2016_8. Epub 2016 Aug 25.

High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient. Rairikar M, Kazi ZB, Desai A, Walters C, Rosenberg A, Kishnani PS. Mol Genet Metab. 2017 Sep;122(1-2):76-79. doi: 10.1016/j.ymgme.2017.05.006. Epub 2017 May 18.

Infantile gangliosidoses: Mapping a timeline of clinical changes. Jarnes Utz JR, Kim S, King K, Ziegler R, Schema L, Redtree ES, Whitley CB. Mol Genet Metab. 2017 Jun;121(2):170-179. doi: 10.1016/j.ymgme.2017.04.011. Epub 2017 Apr 29.

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant. Rairikar MV, Case LE, Bailey LA, Kazi ZB, Desai AK, Berrier KL, Coats J, Gandy R, Quinones R, Kishnani PS. Mol Genet Metab. 2017 Nov;122(3):99-107. doi: 10.1016/j.ymgme.2017.09.008. Epub 2017 Sep 19.

Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I. Nestrasil I, Shapiro E, Svatkova A, Dickson P, Chen A, Wakumoto A, Ahmed A, Stehel E, McNeil S, Gravance C, Maher E. Am J Med Genet A. 2017 Mar;173(3):780-783. doi: 10.1002/ajmg.a.38073.

Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome. Eisengart JB, Jarnes J, Ahmed A, Nestrasil I, Ziegler R, Delaney K, Shapiro E, Whitley C. Mol Genet Metab Rep. 2017 Sep 27;13:64-68. doi: 10.1016/j.ymgmr.2017.07.012. eCollection 2017 Dec.

Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives. Solomon M, Muro S. Adv Drug Deliv Rev. 2017 Sep 1;118:109-134. doi: 10.1016/j.addr.2017.05.004. Epub 2017 May 11.

Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Ou L, Przybilla MJ, Whitley CB. Mol Genet Metab. 2017 Jan-Feb;120(1-2):101-110. doi: 10.1016/j.ymgme.2016.10.001. Epub 2016 Oct 11.

Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment. Mauer M, Sokolovskiy A, Barth JA, Castelli JP, Williams HN, Benjamin ER, Najafian B. J Med Genet. 2017 Nov;54(11):781-786. doi: 10.1136/jmedgenet-2017-104826. Epub 2017 Jul 29.

Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease. Mori M, Haskell G, Kazi Z, Zhu X, DeArmey SM, Goldstein JL, Bali D, Rehder C, Cirulli ET, Kishnani PS. Mol Genet Metab. 2017 Dec;122(4):189-197. doi: 10.1016/j.ymgme.2017.10.008. Epub 2017 Oct 17.

Sustained immune tolerance induction in enzyme replacement therapy-treated CRIM-negative patients with infantile Pompe disease. Kazi ZB, Desai AK, Berrier KL, Troxler RB, Wang RY, Abdul-Rahman OA, Tanpaiboon P, Mendelsohn NJ, Herskovitz E, Kronn D, Inbar-Feigenberg M, Ward-Melver C, Polan M, Gupta P, Rosenberg AS, Kishnani PS. JCI Insight. 2017 Aug 17;2(16):e94328. doi: 10.1172/jci.insight.94328. eCollection 2017 Aug 17.

The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls. Wang RY, Rudser KD, Dengel DR, Braunlin EA, Steinberger J, Jacobs DR, Sinaiko AR, Kelly AS. Int J Mol Sci. 2017 Mar 15;18(3):637. doi: 10.3390/ijms18030637.

A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders. Rappaport J, Manthe RL, Solomon M, Garnacho C, Muro S. Mol Pharm. 2016 Feb 1;13(2):357-368. doi: 10.1021/acs.molpharmaceut.5b00542. Epub 2016 Jan 11.

A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II. Shapiro EG, Rudser K, Ahmed A, Steiner RD, Delaney KA, Yund B, King K, Kunin-Batson A, Eisengart J, Whitley CB. Mol Genet Metab Rep. 2016 Apr 1;7:32-9. doi: 10.1016/j.ymgmr.2016.03.005. eCollection 2016 Jun.

Association of somatic burden of disease with age and neuropsychological measures in attenuated mucopolysaccharidosis types I, II and VI. Ahmed A, Shapiro E, Rudser K, Kunin-Batson A, King K, Whitley CB. Mol Genet Metab Rep. 2016 Apr 1;7:27-31. doi: 10.1016/j.ymgmr.2016.03.006. eCollection 2016 Jun.

Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease). Dyke JP, Sondhi D, Voss HU, Yohay K, Hollmann C, Mancenido D, Kaminsky SM, Heier LA, Rudser KD, Kosofsky B, Casey BJ, Crystal RG, Ballon D. AJNR Am J Neuroradiol. 2016 Jun;37(6):1160-9. doi: 10.3174/ajnr.A4669. Epub 2016 Jan 28.

Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses. Kazi ZB, Prater SN, Kobori JA, Viskochil D, Bailey C, Gera R, Stockton DW, McIntosh P, Rosenberg AS, Kishnani PS. JCI Insight. 2016 Jul 21;1(11):e86821. doi: 10.1172/jci.insight.86821.

Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I. Ou L, Przybilla MJ, Koniar BL, Whitley CB. Mol Genet Metab Rep. 2016 Aug 13;8:87-93. doi: 10.1016/j.ymgmr.2015.11.004. eCollection 2016 Sep.

Elevated TNF-α is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. Polgreen LE, Vehe RK, Rudser K, Kunin-Batson A, Utz JJ, Dickson P, Shapiro E, Whitley CB. Mol Genet Metab. 2016 Apr;117(4):427-30. doi: 10.1016/j.ymgme.2016.01.012. Epub 2016 Jan 28.

Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease. Langan TJ, Barcykowski AL, Dare J, Pannullo EC, Muscarella L, Carter RL. J Neurosci Res. 2016 Nov;94(11):1189-94. doi: 10.1002/jnr.23787.

Hypothyroidism in late-onset Pompe disease. Schneider J, Burmeister LA, Rudser K, Whitley CB, Jarnes Utz J. Mol Genet Metab Rep. 2016 Jul 1;8:24-7. doi: 10.1016/j.ymgmr.2016.06.002. eCollection 2016 Sep.

Immune-Mediated Inflammation May Contribute to the Pathogenesis of Cardiovascular Disease in Mucopolysaccharidosis Type I. Khalid O, Vera MU, Gordts PL, Ellinwood NM, Schwartz PH, Dickson PI, Esko JD, Wang RY. PLoS One. 2016 Mar 17;11(3):e0150850. doi: 10.1371/journal.pone.0150850. eCollection 2016.

Mucopolysaccharidosis (MPS) Physical Symptom Score: Development, Reliability, and Validity. Ahmed A, Rudser K, Kunin-Batson A, Delaney K, Whitley C, Shapiro E. JIMD Rep. 2016;26:61-8. doi: 10.1007/8904_2015_485. Epub 2015 Aug 25.

One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. Najafian B, Tøndel C, Svarstad E, Sokolovkiy A, Smith K, Mauer M. PLoS One. 2016 Apr 15;11(4):e0152812. doi: 10.1371/journal.pone.0152812. eCollection 2016.

The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study. Shapiro E, King K, Ahmed A, Rudser K, Rumsey R, Yund B, Delaney K, Nestrasil I, Whitley C, Potegal M. Mol Genet Metab Rep. 2016 Mar 1;6:41-47. doi: 10.1016/j.ymgmr.2016.01.003.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Parikh S, Bernard G, Leventer RJ, van der Knaap MS, van Hove J, Pizzino A, McNeill NH, Helman G, Simons C, Schmidt JL, Rizzo WB, Patterson MC, Taft RJ, Vanderver A; GLIA Consortium. Mol Genet Metab. 2015 Apr;114(4):501-515. doi: 10.1016/j.ymgme.2014.12.434. Epub 2014 Dec 29.

Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Utz JR, Crutcher T, Schneider J, Sorgen P, Whitley CB. Mol Genet Metab. 2015 Feb;114(2):274-80. doi: 10.1016/j.ymgme.2014.11.015. Epub 2014 Dec 6.

CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. Berrier KL, Kazi ZB, Prater SN, Bali DS, Goldstein J, Stefanescu MC, Rehder CW, Botha EG, Ellaway C, Bhattacharya K, Tylki-Szymanska A, Karabul N, Rosenberg AS, Kishnani PS. Genet Med. 2015 Nov;17(11):912-8. doi: 10.1038/gim.2015.6. Epub 2015 Mar 5.

Case definition and classification of leukodystrophies and leukoencephalopathies. Vanderver A, Prust M, Tonduti D, Mochel F, Hussey HM, Helman G, Garbern J, Eichler F, Labauge P, Aubourg P, Rodriguez D, Patterson MC, Van Hove JL, Schmidt J, Wolf NI, Boespflug-Tanguy O, Schiffmann R, van der Knaap MS; GLIA Consortium. Mol Genet Metab. 2015 Apr;114(4):494-500. doi: 10.1016/j.ymgme.2015.01.006. Epub 2015 Jan 29.

Clinical Laboratory Experience of Blood CRIM Testing in Infantile Pompe Disease. Bali DS, Goldstein JL, Rehder C, Kazi ZB, Berrier KL, Dai J, Kishnani PS. Mol Genet Metab Rep. 2015 Dec 1;5:76-79. doi: 10.1016/j.ymgmr.2015.10.012.

Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. Yund B, Rudser K, Ahmed A, Kovac V, Nestrasil I, Raiman J, Mamak E, Harmatz P, Steiner R, Lau H, Vekaria P, Wozniak JR, Lim KO, Delaney K, Whitley C, Shapiro EG. Mol Genet Metab. 2015 Feb;114(2):170-7. doi: 10.1016/j.ymgme.2014.12.299. Epub 2014 Dec 9.

Consensus statement on preventive and symptomatic care of leukodystrophy patients. Van Haren K, Bonkowsky JL, Bernard G, Murphy JL, Pizzino A, Helman G, Suhr D, Waggoner J, Hobson D, Vanderver A, Patterson MC; GLIA Consortium. Mol Genet Metab. 2015 Apr;114(4):516-26. doi: 10.1016/j.ymgme.2014.12.433. Epub 2014 Dec 27.

Disease specific therapies in leukodystrophies and leukoencephalopathies. Helman G, Van Haren K, Bonkowsky JL, Bernard G, Pizzino A, Braverman N, Suhr D, Patterson MC, Ali Fatemi S, Leonard J, van der Knaap MS, Back SA, Damiani S, Goldman SA, Takanohashi A, Petryniak M, Rowitch D, Messing A, Wrabetz L, Schiffmann R, Eichler F, Escolar ML, Vanderver A; GLIA Consortium. Mol Genet Metab. 2015 Apr;114(4):527-36. doi: 10.1016/j.ymgme.2015.01.014. Epub 2015 Feb 7.

Gene therapy for neurologic manifestations of mucopolysaccharidoses. Wolf DA, Banerjee S, Hackett PB, Whitley CB, McIvor RS, Low WC. Expert Opin Drug Deliv. 2015 Feb;12(2):283-96. doi: 10.1517/17425247.2015.966682. Epub 2014 Dec 16.

Immune Tolerance Strategies in Siblings with Infantile Pompe Disease-Advantages for a Preemptive Approach to High-Sustained Antibody Titers. Stenger EO, Kazi Z, Lisi E, Gambello MJ, Kishnani P. Mol Genet Metab Rep. 2015 Sep 1;4:30-34. doi: 10.1016/j.ymgmr.2015.05.004.

Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment. Shapiro EG, Nestrasil I, Rudser K, Delaney K, Kovac V, Ahmed A, Yund B, Orchard PJ, Eisengart J, Niklason GR, Raiman J, Mamak E, Cowan MJ, Bailey-Olson M, Harmatz P, Shankar SP, Cagle S, Ali N, Steiner RD, Wozniak J, Lim KO, Whitley CB. Mol Genet Metab. 2015 Sep-Oct;116(1-2):61-8. doi: 10.1016/j.ymgme.2015.06.002. Epub 2015 Jun 17.

Neurological aspects of human glycosylation disorders. Freeze HH, Eklund EA, Ng BG, Patterson MC. Annu Rev Neurosci. 2015 Jul 8;38:105-25. doi: 10.1146/annurev-neuro-071714-034019. Epub 2015 Apr 2.

Premature pubarche in children with Pompe disease. Tan QK, Stockton DW, Pivnick E, Choudhri AF, Hines-Dowell S, Pena LD, Deimling MA, Freemark MS, Kishnani PS. J Pediatr. 2015 Apr;166(4):1075-8.e1. doi: 10.1016/j.jpeds.2014.12.074. Epub 2015 Feb 14.

Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo Behavior Rating Scale. Shapiro EG, Nestrasil I, Ahmed A, Wey A, Rudser KR, Delaney KA, Rumsey RK, Haslett PA, Whitley CB, Potegal M. Mol Genet Metab. 2015 Apr;114(4):594-8. doi: 10.1016/j.ymgme.2015.02.008. Epub 2015 Mar 5.

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study. Patterson MC, Mengel E, Vanier MT, Schwierin B, Muller A, Cornelisse P, Pineda M; NPC Registry investigators. Orphanet J Rare Dis. 2015 May 28;10:65. doi: 10.1186/s13023-015-0284-z.

A novel intermediate mucolipidosis II/IIIαβ caused by GNPTAB mutation in the cytosolic N-terminal domain. Leroy JG, Sillence D, Wood T, Barnes J, Lebel RR, Friez MJ, Stevenson RE, Steet R, Cathey SS. Eur J Hum Genet. 2014 May;22(5):594-601. doi: 10.1038/ejhg.2013.207. Epub 2013 Sep 18.

Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. Rumsey RK, Rudser K, Delaney K, Potegal M, Whitley CB, Shapiro E. J Pediatr. 2014 May;164(5):1147-1151.e1. doi: 10.1016/j.jpeds.2014.01.007. Epub 2014 Feb 25.

Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. Stevenson DA, Rudser K, Kunin-Batson A, Fung EB, Viskochil D, Shapiro E, Orchard PJ, Whitley CB, Polgreen LE. J Pediatr Rehabil Med. 2014;7(2):159-65. doi: 10.3233/PRM-140285.

Brave New World. Patterson MC. Child Neurol Open. 2014 Aug 26;1(1):2329048X14542399. doi: 10.1177/2329048X14542399. eCollection 2014 Jul-Sep.

Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness. Wang RY, Braunlin EA, Rudser KD, Dengel DR, Metzig AM, Covault KK, Polgreen LE, Shapiro E, Steinberger J, Kelly AS. Mol Genet Metab. 2014 Feb;111(2):128-32. doi: 10.1016/j.ymgme.2013.11.001. Epub 2013 Nov 12.

Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Polgreen LE, Thomas W, Orchard PJ, Whitley CB, Miller BS. Mol Genet Metab. 2014 Feb;111(2):101-6. doi: 10.1016/j.ymgme.2013.11.013. Epub 2013 Dec 11.

Isokinetic muscle strength differences in patients with mucopolysaccharidosis I, II, and VI. Taylor NE, Dengel DR, Lund TC, Rudser KD, Orchard PJ, Steinberger J, Whitley CB, Polgreen LE. J Pediatr Rehabil Med. 2014;7(4):353-60. doi: 10.3233/PRM-140305.

Letter to the Editors: Concerning "CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy" by Al Khallaf et al. Prater SN, Banugaria SG, Morgan C, Sung CC, Rosenberg AS, Kishnani PS. J Inherit Metab Dis. 2014 Jan;37(1):141-3. doi: 10.1007/s10545-013-9637-8. Epub 2013 Jul 26.

Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. Polgreen LE, Thomas W, Fung E, Viskochil D, Stevenson DA, Steinberger J, Orchard P, Whitley CB, Ensrud KE. J Clin Densitom. 2014 Jan-Mar;17(1):200-6. doi: 10.1016/j.jocd.2013.03.004. Epub 2013 Apr 2.

Lysosomal Disease Network's WORLD Symposium™ 2014. None listed. Mol Genet Metab. 2014 Feb;111(2):S2-6. doi: 10.1016/j.ymgme.2014.01.003. Epub 2014 Jan 9.

Methods of neurodevelopmental assessment in children with neurodegenerative disease: Sanfilippo syndrome. Delaney KA, Rudser KR, Yund BD, Whitley CB, Haslett PA, Shapiro EG. JIMD Rep. 2014;13:129-37. doi: 10.1007/8904_2013_269. Epub 2013 Nov 5.

Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. Mauer M, Glynn E, Svarstad E, Tøndel C, Gubler MC, West M, Sokolovskiy A, Whitley C, Najafian B. PLoS One. 2014 Nov 11;9(11):e112188. doi: 10.1371/journal.pone.0112188. eCollection 2014.

Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the α-L-iduronidase gene in Hurler-Scheie syndrome. Ahmed A, Whitley CB, Cooksley R, Rudser K, Cagle S, Ali N, Delaney K, Yund B, Shapiro E. Mol Genet Metab. 2014 Feb;111(2):123-7. doi: 10.1016/j.ymgme.2013.11.014. Epub 2013 Dec 12.

Quantitative neuroimaging in mucolipidosis type IV. Schiffmann R, Mayfield J, Swift C, Nestrasil I. Mol Genet Metab. 2014 Feb;111(2):147-51. doi: 10.1016/j.ymgme.2013.11.007. Epub 2013 Nov 21.

Risk of death in heart disease is associated with elevated urinary globotriaosylceramide. Schiffmann R, Forni S, Swift C, Brignol N, Wu X, Lockhart DJ, Blankenship D, Wang X, Grayburn PA, Taylor MR, Lowes BD, Fuller M, Benjamin ER, Sweetman L. J Am Heart Assoc. 2014 Feb 4;3(1):e000394. doi: 10.1161/JAHA.113.000394.

Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. Banugaria SG, Prater SN, Patel TT, Dearmey SM, Milleson C, Sheets KB, Bali DS, Rehder CW, Raiman JA, Wang RA, Labarthe F, Charrow J, Harmatz P, Chakraborty P, Rosenberg AS, Kishnani PS. PLoS One. 2013 Jun 25;8(6):e67052. doi: 10.1371/journal.pone.0067052. Print 2013.

Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging. Dyke JP, Sondhi D, Voss HU, Shungu DC, Mao X, Yohay K, Worgall S, Hackett NR, Hollmann C, Yeotsas ME, Jeong AL, Van de Graaf B, Cao I, Kaminsky SM, Heier LA, Rudser KD, Souweidane MM, Kaplitt MG, Kosofsky B, Crystal RG, Ballon D. AJNR Am J Neuroradiol. 2013 Apr;34(4):884-9. doi: 10.3174/ajnr.A3297. Epub 2012 Oct 4.

Basilar artery aneurysm: a new finding in classic infantile Pompe disease. Patel TT, Banugaria SG, Frush DP, Enterline DS, Tanpaiboon P, Kishnani PS. Muscle Nerve. 2013 Apr;47(4):613-5. doi: 10.1002/mus.23659. Epub 2013 Feb 10.

Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions. Dolisca SB, Mehta M, Pearce DA, Mink JW, Maria BL. J Child Neurol. 2013 Sep;28(9):1074-100. doi: 10.1177/0883073813493665. Epub 2013 Jul 9.

Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease. Banugaria SG, Prater SN, McGann JK, Feldman JD, Tannenbaum JA, Bailey C, Gera R, Conway RL, Viskochil D, Kobori JA, Rosenberg AS, Kishnani PS. Genet Med. 2013 Feb;15(2):123-31. doi: 10.1038/gim.2012.110. Epub 2012 Oct 11.

Classification and natural history of the neuronal ceroid lipofuscinoses. Mink JW, Augustine EF, Adams HR, Marshall FJ, Kwon JM. J Child Neurol. 2013 Sep;28(9):1101-5. doi: 10.1177/0883073813494268. Epub 2013 Jul 9.

Clinical trials in rare disease: challenges and opportunities. Augustine EF, Adams HR, Mink JW. J Child Neurol. 2013 Sep;28(9):1142-50. doi: 10.1177/0883073813495959.

Enzyme replacement is associated with better cognitive outcomes after transplant in Hurler syndrome. Eisengart JB, Rudser KD, Tolar J, Orchard PJ, Kivisto T, Ziegler RS, Whitley CB, Shapiro EG. J Pediatr. 2013 Feb;162(2):375-80.e1. doi: 10.1016/j.jpeds.2012.07.052. Epub 2012 Sep 10.

Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients. Vera M, Le S, Kan SH, Garban H, Naylor D, Mlikotic A, Kaitila I, Harmatz P, Chen A, Dickson P. Pediatr Res. 2013 Dec;74(6):712-20. doi: 10.1038/pr.2013.158. Epub 2013 Sep 3.

Lysosomal Disease Network's WORLD Symposium™ 2013. Whitley C. Mol Genet Metab. 2013 Feb;108(2):S2-7. doi: 10.1016/j.ymgme.2012.12.003. Epub 2012 Dec 25.

Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates. de Blieck EA, Augustine EF, Marshall FJ, Adams H, Cialone J, Dure L, Kwon JM, Newhouse N, Rose K, Rothberg PG, Vierhile A, Mink JW; Batten Study Group. Contemp Clin Trials. 2013 Jul;35(2):48-54. doi: 10.1016/j.cct.2013.04.004. Epub 2013 Apr 26.

Mucopolysaccharidosis Type IIIA presents as a variant of Klüver-Bucy syndrome. Potegal M, Yund B, Rudser K, Ahmed A, Delaney K, Nestrasil I, Whitley CB, Shapiro EG. J Clin Exp Neuropsychol. 2013;35(6):608-16. doi: 10.1080/13803395.2013.804035. Epub 2013 Jun 8.

N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Öz G, Cloyd JC, Tuite PJ. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713.

NCL diseases - clinical perspectives. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. Biochim Biophys Acta. 2013 Nov;1832(11):1801-6. doi: 10.1016/j.bbadis.2013.04.008. Epub 2013 Apr 17.

Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). Adams HR, Mink JW; University of Rochester Batten Center Study Group. J Child Neurol. 2013 Sep;28(9):1128-36. doi: 10.1177/0883073813494813.

Renal complications of Fabry disease in children. Najafian B, Mauer M, Hopkin RJ, Svarstad E. Pediatr Nephrol. 2013 May;28(5):679-87. doi: 10.1007/s00467-012-2222-9. Epub 2012 Aug 17.

An exploratory study of brain function and structure in mucopolysaccharidosis type I: long term observations following hematopoietic cell transplantation (HCT). Shapiro E, Guler OE, Rudser K, Delaney K, Bjoraker K, Whitley C, Tolar J, Orchard P, Provenzale J, Thomas KM. Mol Genet Metab. 2012 Sep;107(1-2):116-21. doi: 10.1016/j.ymgme.2012.07.016. Epub 2012 Jul 20.

Females experience a more severe disease course in Batten disease. Cialone J, Adams H, Augustine EF, Marshall FJ, Kwon JM, Newhouse N, Vierhile A, Levy E, Dure LS, Rose KR, Ramirez-Montealegre D, de Blieck EA, Mink JW. J Inherit Metab Dis. 2012 May;35(3):549-55. doi: 10.1007/s10545-011-9421-6. Epub 2011 Dec 14.

Lysosomal Disease Network's WORLD Symposium™ 2012. Whitley CB. Mol Genet Metab. 2012 Feb;105(2):S3-6. doi: 10.1016/j.ymgme.2011.12.001. Epub 2011 Dec 7.

Neurology of inherited glycosylation disorders. Freeze HH, Eklund EA, Ng BG, Patterson MC. Lancet Neurol. 2012 May;11(5):453-66. doi: 10.1016/S1474-4422(12)70040-6.

Persistence of high sustained antibodies to enzyme replacement therapy despite extensive immunomodulatory therapy in an infant with Pompe disease: need for agents to target antibody-secreting plasma cells. Banugaria SG, Patel TT, Mackey J, Das S, Amalfitano A, Rosenberg AS, Charrow J, Chen YT, Kishnani PS. Mol Genet Metab. 2012 Apr;105(4):677-80. doi: 10.1016/j.ymgme.2012.01.019. Epub 2012 Jan 28.

Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis. Lo SM, Choi M, Liu J, Jain D, Boot RG, Kallemeijn WW, Aerts JM, Pashankar F, Kupfer GM, Mane S, Lifton RP, Mistry PK. Blood. 2012 May 17;119(20):4731-40. doi: 10.1182/blood-2011-10-386862. Epub 2012 Apr 4.

Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. Bali DS, Goldstein JL, Banugaria S, Dai J, Mackey J, Rehder C, Kishnani PS. Am J Med Genet C Semin Med Genet. 2012 Feb 15;160C(1):40-9. doi: 10.1002/ajmg.c.31319. Epub 2012 Jan 17.

Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Messinger YH, Mendelsohn NJ, Rhead W, Dimmock D, Hershkovitz E, Champion M, Jones SA, Olson R, White A, Wells C, Bali D, Case LE, Young SP, Rosenberg AS, Kishnani PS. Genet Med. 2012 Jan;14(1):135-42. doi: 10.1038/gim.2011.4.

The emerging phenotype of long-term survivors with infantile Pompe disease. Prater SN, Banugaria SG, DeArmey SM, Botha EG, Stege EM, Case LE, Jones HN, Phornphutkul C, Wang RY, Young SP, Kishnani PS. Genet Med. 2012 Sep;14(9):800-10. doi: 10.1038/gim.2012.44. Epub 2012 Apr 26.

An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions. El-Gharbawy AH, Mackey J, DeArmey S, Westby G, Grinnell SG, Malovrh P, Conway R, Kishnani PS. Mol Genet Metab. 2011 Sep-Oct;104(1-2):118-22. doi: 10.1016/j.ymgme.2011.07.004. Epub 2011 Jul 13.

Atypical immunologic response in a patient with CRIM-negative Pompe disease. Abbott MA, Prater SN, Banugaria SG, Richards SM, Young SP, Rosenberg AS, Kishnani PS. Mol Genet Metab. 2011 Dec;104(4):583-6. doi: 10.1016/j.ymgme.2011.08.003. Epub 2011 Aug 11.

Intrathecal enzyme replacement therapy for mucopolysaccharidosis I: translating success in animal models to patients. Dickson PI, Chen AH. Curr Pharm Biotechnol. 2011 Jun;12(6):946-55. doi: 10.2174/138920111795542642.

Mucolipidosis type III α/β: the first characterization of this rare disease by autopsy. Kerr DA, Memoli VA, Cathey SS, Harris BT. Arch Pathol Lab Med. 2011 Apr;135(4):503-10. doi: 10.5858/2010-0236-CR.1.

Natural history of infantile G(M2) gangliosidosis. Bley AE, Giannikopoulos OA, Hayden D, Kubilus K, Tifft CJ, Eichler FS. Pediatrics. 2011 Nov;128(5):e1233-41. doi: 10.1542/peds.2011-0078. Epub 2011 Oct 24.

Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data. Cialone J, Augustine EF, Newhouse N, Adams H, Vierhile A, Marshall FJ, de Blieck EA, Kwon J, Rothberg PG, Mink JW. J Inherit Metab Dis. 2011 Oct;34(5):1075-81. doi: 10.1007/s10545-011-9346-0. Epub 2011 May 10.

Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Najafian B, Svarstad E, Bostad L, Gubler MC, Tøndel C, Whitley C, Mauer M. Kidney Int. 2011 Mar;79(6):663-670. doi: 10.1038/ki.2010.484. Epub 2010 Dec 15.

Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease). Kwon JM, Adams H, Rothberg PG, Augustine EF, Marshall FJ, Deblieck EA, Vierhile A, Beck CA, Newhouse NJ, Cialone J, Levy E, Ramirez-Montealegre D, Dure LS, Rose KR, Mink JW. Neurology. 2011 Nov 15;77(20):1801-7. doi: 10.1212/WNL.0b013e318237f649. Epub 2011 Oct 19.

Quantitating glomerular endothelial fenestration: an unbiased stereological approach. Najafian B, Mauer M. Am J Nephrol. 2011;33 Suppl 1(Suppl 1):34-9. doi: 10.1159/000327075. Epub 2011 Jun 10.

Quantitative telemedicine ratings in Batten disease: implications for rare disease research. Cialone J, Augustine EF, Newhouse N, Vierhile A, Marshall FJ, Mink JW. Neurology. 2011 Nov 15;77(20):1808-11. doi: 10.1212/WNL.0b013e3182377e29. Epub 2011 Oct 19.

Research challenges in central nervous system manifestations of inborn errors of metabolism. Dickson PI, Pariser AR, Groft SC, Ishihara RW, McNeil DE, Tagle D, Griebel DJ, Kaler SG, Mink JW, Shapiro EG, Bjoraker KJ, Krivitzky L, Provenzale JM, Gropman A, Orchard P, Raymond G, Cohen BH, Steiner RD, Goldkind SF, Nelson RM, Kakkis E, Patterson MC. Mol Genet Metab. 2011 Mar;102(3):326-38. doi: 10.1016/j.ymgme.2010.11.164. Epub 2010 Dec 2.

The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease. Banugaria SG, Prater SN, Ng YK, Kobori JA, Finkel RS, Ladda RL, Chen YT, Rosenberg AS, Kishnani PS. Genet Med. 2011 Aug;13(8):729-36. doi: 10.1097/GIM.0b013e3182174703.

Towards a selected reaction monitoring mass spectrometry fingerprint approach for the screening of oligosaccharidoses. Sowell J, Wood T. Anal Chim Acta. 2011 Feb 7;686(1-2):102-6. doi: 10.1016/j.aca.2010.11.047. Epub 2010 Dec 7.

Assessment of renal pathology and dysfunction in children with Fabry disease. Ramaswami U, Najafian B, Schieppati A, Mauer M, Bichet DG. Clin J Am Soc Nephrol. 2010 Feb;5(2):365-70. doi: 10.2215/CJN.08091109. Epub 2010 Jan 7.

Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Kishnani PS, Goldenberg PC, DeArmey SL, Heller J, Benjamin D, Young S, Bali D, Smith SA, Li JS, Mandel H, Koeberl D, Rosenberg A, Chen YT. Mol Genet Metab. 2010 Jan;99(1):26-33. doi: 10.1016/j.ymgme.2009.08.003.

Growth patterns and the use of growth hormone in the mucopolysaccharidoses. Polgreen LE, Miller BS. J Pediatr Rehabil Med. 2010;3(1):25-38. doi: 10.3233/PRM-2010-0106.

Movers and shakers: diagnosing neurotransmitter diseases with CSF. Patterson MC. Neurology. 2010 Jul 6;75(1):15-7. doi: 10.1212/WNL.0b013e3181e9aeea. Epub 2010 Jun 9.

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo M, Stevenson RE, Friez MJ. J Med Genet. 2010 Jan;47(1):38-48. doi: 10.1136/jmg.2009.067736. Epub 2009 Jul 16.

The natural history and osteodystrophy of mucolipidosis types II and III. David-Vizcarra G, Briody J, Ault J, Fietz M, Fletcher J, Savarirayan R, Wilson M, McGill J, Edwards M, Munns C, Alcausin M, Cathey S, Sillence D. J Paediatr Child Health. 2010 Jun;46(6):316-22. doi: 10.1111/j.1440-1754.2010.01715.x. Epub 2010 Mar 29.

A Noncanonical CD56dimCD16dim/− NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases. Yandamuri SS, Filipek B, Lele N, Cohen I, Bennett JL, Nowak RJ, Sotirchos ES, Longbrake EE, Mace EM, O'Connor KC. J Immunol. 2024 Mar 1;212(5):785-800. doi: 10.4049/jimmunol.2300015. PMID: 38251887; PMCID: PMC10932911.

Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein Ab disease, and autoimmune myasthenia gravis (MG) are autoantibody-mediated autoimmune diseases. Autoantibodies can cause a type of immune reaction called Ab-dependent cellular cytotoxicity (ADCC) involving natural killer (NK) cells. However, it is not known whether ADCC contributes to disease development in patients with these conditions.

In this study, researchers investigated the characteristics of circulating NK cells in patients with NMOSD, myelin oligodendrocyte glycoprotein Ab disease, and MG. The team used functional assays, phenotyping, and transcriptomics to explore the role of NK cells in these diseases.

Results show elevated subsets of NK cells in patients with NMOSD and MG. Authors note that this elevation suggests prior ADCC activity occurring in the affected tissues.

Myasthenia gravis: the changing treatment landscape in the era of molecular therapies. Iorio R. Nat Rev Neurol. 2024 Feb;20(2):84-98. doi: 10.1038/s41582-023-00916-w. Epub 2024 Jan 8. PMID: 38191918.

Myasthenia gravis (MG) is a rare neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) or muscle-specific kinase (MuSK) on muscles. To date, the standard therapy for MG has relied on acetylcholinesterase inhibitors, corticosteroids, and immunosuppressants. These therapies have shown good efficacy in improving MG-related symptoms in most individuals. However, they can also cause long-term adverse effects, and up to 15% of individuals with MG show limited or no response.

This review paper provides a comprehensive overview of emerging molecular therapies for MG. The author discusses progress in therapies associated with AChR antibodies and MuSK antibodies, including both challenges and opportunities.

The author notes that molecular therapies have the potential to revolutionize the MG treatment landscape, unlocking new potential for personalized medicine approaches.

A Digital Telehealth System to Compute Myasthenia Gravis Core Examination Metrics: Exploratory Cohort Study. Garbey M, Joerger G, Lesport Q, Girma H, McNett S, Abu-Rub M, Kaminski H. JMIR Neurotechnol. 2023;2:e43387. doi: 10.2196/43387. Epub 2023 Apr 19. PMID: 37435094; PMCID: PMC10334459

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Recently, telemedicine practices have grown for neurological diseases, including MG. Telemedicine evaluation of patients with MG has been recommended via the Myasthenia Gravis Core Examination (MG-CE).

In this study, researchers developed a new telehealth system to automate data acquisition and analytics during the MG-CE. Using Zoom videos of patients with MG undergoing the MG-CE, the team created an algorithm toolbox—including computer vision and signal processing methods—to analyze eye motions, body motions, and vocalizations.  

Results show that this new system can objectively quantitate metrics from the MG-CE, allowing the medical examiner to concentrate on the patient instead of managing logistics. Authors note that the system could also be applied to many other neurological disorders, potentially improving clinical care.

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials. Guptill JT, Benatar M, Granit V, Habib AA, Howard JF, Barnett-Tapia C, Nowak RJ, Lee I, Ruzhansky K, Dimachkie MM, Cutter GR, Kaminski HJ. Neurology. 2023 Apr 19;10.1212/WNL.0000000000207278. doi: 10.1212/WNL.0000000000207278. Online ahead of print.

Clinicoserological insights into patients with immune checkpoint inhibitor-induced myasthenia gravis. Masi G, Pham MC, Karatz T, Oh S, Payne AS, Nowak RJ, Howard JF Jr, Guptill JT, Juel VC, O'Connor KC. Ann Clin Transl Neurol. 2023 May;10(5):825-831. doi: 10.1002/acn3.51761. Epub 2023 Mar 16.

Comparison of Fixed and Live Cell-Based Assay for the Detection of AChR and MuSK Antibodies in Myasthenia Gravis. Spagni G, Gastaldi M, Businaro P, Chemkhi Z, Carrozza C, Mascagna G, Falso S, Scaranzin S, Franciotta D, Evoli A, Damato V. Neurol Neuroimmunol Neuroinflamm. 2022 Oct 21;10(1):e200038. doi: 10.1212/NXI.0000000000200038. PMID: 36270951; PMCID: PMC9621337.

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) in muscles. Double seronegative myasthenia gravis (dSN-MG) is a type of MG where patients do not have detectable AChRs or muscle-specific tyrosine kinase (MuSK) antibodies, which are two of the most common antibody markers for MG. In some patients with dSN-MG, a technique called cell-based assay (CBA) can be used to detect these antibodies. However, research comparing fixed and live CBA is lacking.

In this study, the research group of MGNet Pilot Awardee Valentina Damato, MD, PhD, compared the performance of fixed and live CBAs in serum samples from 192 patients with radioimmunoassay (RIA)-dSN-MG and 100 control subjects. The team also assessed the sensitivity and specificity of these techniques in RIA-positive MG samples.

Results show that fixed CBA represents a valuable alternative to RIA for AChR and MuSK antibody detection in patients with MG. Authors note that fixed CBA could be considered as a first-step diagnostic test, while live CBA can be useful in serologic testing of RIA- and fixed CBA-negative samples.

Editorial: Global excellence in inflammatory diseases: North America 2021. Kusner LL, Misra RS, Lucas R. Front Immunol. 2023 Jul 6;14:1245827. doi: 10.3389/fimmu.2023.1245827. eCollection 2023.

Eye Segmentation Method for Telehealth: Application to the Myasthenia Gravis Physical Examination. Lesport Q, Joerger G, Kaminski HJ, Girma H, McNett S, Abu-Rub M, Garbey M. Sensors (Basel). 2023 Sep 7;23(18):7744. doi: 10.3390/s23187744. PMID: 37765800; PMCID: PMC10536520

Myasthenia gravis (MG) is a neuromuscular disorder which produces muscle weakness that can worsen over the course of a minute during an examination. Use of telemedicine has recently increased for monitoring MG, although these evaluations rely entirely on subjective evaluations of an examiner.

In this study, researchers developed a new telehealth platform to assist with telemedicine evaluations of ocular manifestations of patients with MG. The team created a hybrid algorithm that combines deep learning with computer vision, giving quantitative metrics of ptosis (eyelid droop) and ocular muscle fatigue leading to symptoms like double vision.

The method, which works on both a fixed image and frame by frame of the video in real-time, is able to operate in standard telehealth conditions. Authors note that this approach is general and can be applied to many disorders of ocular motility and ptosis.

Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology. Pham MC, Masi G, Patzina R, Obaid AH, Oxendine SR, Oh S, Payne AS, Nowak RJ, O'Connor KC. Acta Neuropathol. 2023 Aug;146(2):319-336. doi: 10.1007/s00401-023-02603-y. Epub 2023 Jun 21. PMID: 37344701

In patients with myasthenia gravis (MG), an autoimmune response blocks or damages acetylcholine receptors in muscles. Autoantibody clones drive three different pathogenic (disease-causing) mechanisms of MG, including complement activation, receptor blockade, and antigenic modulation. However, it is unclear whether these mechanisms are driven by single or multiple antibody clones.

In this study, researchers investigated the ability of individual autoantibody clones to drive multiple pathogenic mechanisms of MG. First, the team produced monoclonal autoantibodies (mAbs) from patients with MG. Next, researchers assessed the binding properties and pathogenic capacities of the mAbs.

Results show that these mAbs can drive pathology through blocking the acetylcholine binding site, internalizing the AChR through crosslinking (modulation), and activating complement. While some mAbs can drive one or two of these mechanisms, several mAbs were able to drive all three simultaneously. Authors note that these new insights on the immunopathology of MG could help inform therapeutic approaches.

MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. Yandamuri SS, Filipek B, Obaid AH, Lele N, Thurman JM, Makhani N, Nowak RJ, Guo Y, Lucchinetti CF, Flanagan EP, Longbrake EE, O'Connor KC. JCI Insight. 2023 Jun 8;8(11):e165373. doi: 10.1172/jci.insight.165373.

Measuring Overall Severity of Myasthenia Gravis (MG): Evidence for the Added Value of the MG Symptoms PRO. Regnault A, Morel T, de la Loge C, Mazerolle F, Kaminski HJ, Habib AA. Neurol Ther. 2023 Oct;12(5):1573-1590. doi: 10.1007/s40120-023-00464-x. Epub 2023 May 11.

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi EJ, Alvarado A, Cottman-Thomas E, Maseda D, Tsao PY, Ellebrecht CT, Khella SL, Richman DP, O'Connor KC, Herzberg U, Binder GK, Milone MC, Basu S, Payne AS. Nat Biotechnol. 2023 Sep;41(9):1229-1238. doi: 10.1038/s41587-022-01637-z. Epub 2023 Jan 19.

Remission of severe myasthenia gravis after autologous stem cell transplantation. Schlatter MI, Yandamuri SS, O'Connor KC, Nowak RJ, Pham MC, Obaid AH, Redman C, Provost M, McSweeney PA, Pearlman ML, Tees MT, Bowen JD, Nash RA, Georges GE. Ann Clin Transl Neurol. 2023 Sep 19. doi: 10.1002/acn3.51898. Epub ahead of print. PMID: 37726935

Myasthenia gravis (MG) is a rare neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) on muscles. High-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT), also known as bone marrow transplant, are potential treatments for MG.

In this study, researchers investigated the safety and efficacy of HDIT and HCT in a patient with severe, treatment-resistant MG. Results show that HDIT and HCT induced remission of MG. The team also assessed the effect of treatment on the underlying immunopathology. Intriguingly, the AChR autoantibodies—the known pathogenic mediators of MG—did not appreciably lower after the treatment.

Authors state that these findings suggest a cell-based disease mechanism, which responds to high-dose therapy, may play a role in the pathology in addition to AChR autoantibodies. Further studies are needed to establish whether HDIT and HCT can be an effective therapy for severe MG.

Serum metabolomics of treatment response in myasthenia gravis. Sikorski P, Li Y, Cheema M, Wolfe GI, Kusner LL, Aban I, Kaminski HJ. PLoS One. 2023 Oct 10;18(10):e0287654. doi: 10.1371/journal.pone.0287654. PMID: 37816000; PMCID: PMC10564178

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. The primary initial therapy for MG is high-dose prednisone use. However, more than a third of patients do not respond to this treatment. Currently, there are no biomarkers to predict clinical responsiveness to corticosteroid treatment.

In this study, researchers defined a treatment-responsive biomarker for MG patients undergoing corticosteroid therapy. The team used serum from MG patients collected for a clinical trial of thymectomy (removal of the thymus gland) and prednisone to create metabolomic and lipidomic profiles. Next, researchers correlated these profiles with treatment response.

Results show that metabolomic and lipidomic profiles could be used to predict treatment response. Authors note that variation in prednisone metabolism may determine how well patients respond to treatment.

A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2). Guptill JT, Nowak RJ, Guidon AC, Howard JF, Soliven B, Hammett A, Munro Sheldon B, Li Y, Meece T, Aban I, Cutter G, Kaminski HJ, and the EXPLORE-MG2 Study Team. Neurology. 2022 April P.6005. [Presented as poster at the 2022 American Academy of Neurology (AAN) Annual Meeting in Seattle, WA  April 2022.]

A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2). Guptill JT, Nowak RJ, Guidon AC, Howard JF, Soliven B, Hammett A, Munro Sheldon B, Li Y, Meece T, Aban I, Cutter G, Kaminski HJ, and the EXPLORE-MG2 Study Team. Muscle Nerve. 2022 May 65:S1;S7-S8. [Presented as poster at the 14th MGFA International Conference on Myasthenia and Related Disorders in Miami, Florida in May 2022.]

Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis (ADAPT-teleMG): An Innovation in Rare Disesae Study Design During the COVID-19 Pandemic. Guidon AC, Guptill JT, Aban I, Cutter G, Soliven B, Benatar M, Kaminski HJ, Nowak RJ, on behalf of MGNet. Muscle Nerve. 2022 May. [Presented as poster at the 14th MGFA International Conference on Myasthenia and Related Disorders in Miami, Florida in May 2022, Presented at the EveryLife Foundation for Rare Diseases 2020 Scientific Workshop.]

Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders. Verschuuren JJ, Palace J, Murai H, Tannemaat MR, Kaminski HJ, Bril V. Lancet Neurol. 2022 Feb;21(2):189-202. doi: 10.1016/S1474-4422(21)00463-4. Erratum in: Lancet Neurol. 2022 Mar;21(3):e3. PMID: 35065041.

Henry Kaminski, MD, principal investigator of the Myasthenia Gravis Rare Disease Network (MGNet), and his colleagues have published a review of the present-day therapy for the autoimmune disease myasthenia gravis (MG). Despite there being only 120,000 patients with MG in the US, the well-understood pathophysiology provides a testing ground for drug development to reduce pathogenic antibody in circulation and for B cell depletion to target autoreactive cells. This review paper discusses a new class of agent, FcRn inhibitors, as well as complement inhibitors, which have recently been approved by the US Food and Drug Administration for use in MG. Challenges remain as a cure remains an elusive goal.

Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. Damato V, Spagni G, Monte G, Woodhall M, Jacobson L, Falso S, Smith T, Iorio R, Waters P, Irani SR, Vincent A, Evoli A. J Neurol Neurosurg Psychiatry. 2022 Sep;93(9):995-1000. doi: 10.1136/jnnp-2022-329284. Epub 2022 Jul 14.

Corticosteroid Treatment-Resistance in Myasthenia Gravis. Kaminski HJ, Denk J. Front Neurol. 2022 Apr 25;13:886625. doi: 10.3389/fneur.2022.886625. eCollection 2022.

Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis. Obaid AH, Zografou C, Vadysirisack DD, Munro-Sheldon B, Fichtner ML, Roy B, Philbrick WM, Bennett JL, Nowak RJ, O'Connor KC. Neurol Neuroimmunol Neuroinflamm. 2022 Apr 26;9(4):e1169. doi: 10.1212/NXI.0000000000001169. PMID: 35473886.

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Clinical assays—laboratory tests used to diagnose and monitor patients—only measure autoantibody binding. Therefore, these tests often provide limited insight on disease burden and therapeutic response. To address these limitations, Dr. Kevin C. O’Connor and colleagues at Yale University developed a new assay for evaluating acetylcholine receptor autoantibody–mediated complement activity. Results suggested that a subset of patients lacks association between membrane attack complex formation and autoantibody binding or disease burden. Authors note that this assay provides a better understanding of autoantibody mechanisms and may improve predictions for treatment response. Ultimately, these measurements could help assess disease progression and provide more individualized treatment plans.

Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study. Chia R, Saez-Atienzar S, Murphy N, Chiò A, Blauwendraat C; International Myasthenia Gravis Genomics Consortium, Roda RH, Tienari PJ, Kaminski HJ, Ricciardi R, Guida M, De Rosa A, Petrucci L, Evoli A, Provenzano C, Drachman DB, Traynor BJ. Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2108672119. doi: 10.1073/pnas.2108672119.

Myasthenia gravis complement activity is independent of autoantibody titer and disease severity. Fichtner ML, Hoarty MD, Vadysirisack DD, Munro-Sheldon B, Nowak RJ, O'Connor KC. PLoS One. 2022 Mar 15;17(3):e0264489. doi: 10.1371/journal.pone.0264489. eCollection 2022.

Novel pathophysiological insights in autoimmune myasthenia gravis. Masi G, O'Connor KC. Curr Opin Neurol. 2022 Aug 5. doi: 10.1097/WCO.0000000000001088. Epub ahead of print. PMID: 35942663.

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Affected receptors cannot properly receive nerve signals, impacting voluntary muscle contractions. Generalized muscle weakness and fatigue with prolonged activity are characteristic symptoms, which improve with rest. In this review article, authors summarize recent insights into the development of MG relating to the immune system, including the mechanisms of various MG disease subtypes. They also describe the wide range of treatment options now available to patients with MG, which have uncovered significant differences in clinical responses between subtypes. These differences could help clinicians choose specific therapeutic strategies. Authors conclude that improved understanding of autoantibodies is revealing the mechanisms that guide the development of MG. In the future, authors note that studies on the differences in immunology among MG patients will be key to developing effective, individualized therapies.

Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O'Connor KC. Acta Neuropathol Commun. 2022 Oct 28;10(1):154. doi: 10.1186/s40478-022-01454-0. PMID: 36307868; PMCID: PMC9617453.

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. A small number of individuals with MG have autoantibodies that target muscle-specific tyrosine kinase (MuSK), which is an enzyme that is crucial to the development and maintenance of the neuromuscular junction. Most patients with MuSK MG can experience remission with CD20-mediated B cell depletion therapy (BCDT). However, relapse is common. In this study, researchers explored the factors that lead to relapse after BCDT in patients with MuSK MG. The team studied autoantibody-producing B cells over the course of BCDT, identifying MuSK-specific B cells from nine patients. Researchers isolated two MuSK-specific B cells from two patients who were experiencing relapse after BCDT. Next, the team explored the molecular properties of these B cells and collected longitudinal samples from the patients. Findings showed that a reservoir of pathogenic, autoantibody-producing B cell clones survived BCDT and reemerged several months before relapse. Authors state that this study provides a better understanding of MuSK MG relapse, as well as a possible biomarker for relapse prediction.

The best and worst of times in therapy development for myasthenia gravis. Benatar M, Cutter G, Kaminski HJ. Muscle Nerve. 2022 Nov 2. doi: 10.1002/mus.27742. Epub ahead of print. PMID: 36321730.

Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. The US Federal Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN)-inhibitors, a type of therapy for autoimmune diseases, for treatment of MG. Several other therapies are also in late stage clinical trials or under regulatory review. However, questions remain about which patients are most likely to benefit from which therapies and how effective the treatments will be. In this review article, researchers discuss therapy development for MG, including the most critical needs for clinical trial readiness and biomarker development. Authors provide a summary of Myasthenia Gravis Rare Disease Network (MGNet) meetings held during the MG Foundation of America International Conference, where these topics were discussed. Authors conclude with a series of recommendations to guide focused research in the most critical areas of therapy development for MG, welcoming ongoing discussion.

The clinical need for clustered AChR cell-based assay testing of seronegative MG. Masi G, Li Y, Karatz T, Pham MC, Oxendine SR, Nowak RJ, Guptill JT, O'Connor KC. J Neuroimmunol. 2022 Jun 15;367:577850. doi: 10.1016/j.jneuroim.2022.577850. Epub 2022 Mar 25.

Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease. Cleanthous S, Mork AC, Regnault A, Cano S, Kaminski HJ, Morel T. Orphanet J Rare Dis. 2021 Oct 30;16(1):457. doi: 10.1186/s13023-021-02064-0.

Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes. Mandel-Brehm C, Fichtner ML, Jiang R, Winton VJ, Vazquez SE, Pham MC, Hoehn KB, Kelleher NL, Nowak RJ, Kleinstein SH, Wilson MR, DeRisi JL, O'Connor KC. J Immunol. 2021 Oct 15;207(8):2005-2014. doi: 10.4049/jimmunol.2100225. Epub 2021 Sep 20.

Myasthenia gravis (MG) is a B cell mediated autoimmune disorder that affects neuromuscular transmission. Patients with MG experience severe muscle weakness and increased fatigability. MG pathology is directly facilitated by IgG isotype autoantibodies. Diversity of immunoglobin G V regions (IgG-Vs) is critical for immunity. Recently, the presence of N-linked glycosylation of IgG-Vs (IgG-VN-Glyc) has been shown to contribute to diversity. In autoimmune disorders, researchers have observed higher frequencies of IgG-VN-Glyc when compared to healthy individuals. To test the boarder specificity of elevated IgG-VN-Glyc, MGNet investigators studied patients with distinct subtypes of MG: AChR and MuSK. The investigators focused on examining the B cell repertoire and total IgG, applying complementary sequencing and proteomic-based approaches. When compared with healthy donors, MGNet investigators found that the frequency of IgG-VN-Glyc motifs was increased in the total B cell receptor (BCR) repertoire of patients with MG. The investigators also found that the fraction of total IgG-VN-Glyc in MG serum is elevated, and the presence of IgG-VN-Glyc did not alter binding of several MG patient-derived monoclonal antibodies (mAbs). These findings contribute to efforts to understand the basic biology of IgG-VN-Glyc and its association with disease.

Telemedicine visits in myasthenia gravis: Expert guidance and the Myasthenia Gravis Core Exam (MG-CE). Guidon AC, Muppidi S, Nowak RJ, Guptill JT, Hehir MK, Ruzhansky K, Burton LB, Post D, Cutter G, Conwit R, Mejia NI, Kaminski HJ, Howard JF Jr. Muscle Nerve. 2021 Sep;64(3):270-276. doi: 10.1002/mus.27260. Epub 2021 Jul 7.

Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis. Fichtner ML, Vieni C, Redler RL, Kolich L, Jiang R, Takata K, Stathopoulos P, Suarez PA, Nowak RJ, Burden SJ, Ekiert DC, O'Connor KC. J Exp Med. 2020 Dec 7;217(12):e20200513. doi: 10.1084/jem.20200513.

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology. Fichtner ML, Jiang R, Bourke A, Nowak RJ, O'Connor KC. Front Immunol. 2020 May 27;11:776. doi: 10.3389/fimmu.2020.00776. eCollection 2020.

Complement Inhibitor Therapy for Myasthenia Gravis. Albazli K, Kaminski HJ, Howard JF Jr. Front Immunol. 2020 Jun 3;11:917. doi: 10.3389/fimmu.2020.00917. eCollection 2020.

Epidemiological evidence for a hereditary contribution to myasthenia gravis: a retrospective cohort study of patients from North America. Green JD, Barohn RJ, Bartoccion E, Benatar M, Blackmore D, Chaudhry V, Chopra M, Corse A, Dimachkie MM, Evoli A, Florence J, Freimer M, Howard JF, Jiwa T, Kaminski HJ, Kissel JT, Koopman WJ, Lipscomb B, Maestri M, Marino M, Massey JM, McVey A, Mezei MM, Muppidi S, Nicolle MW, Oger J, Pascuzzi RM, Pasnoor M, Pestronk A, Provenzano C, Ricciardi R, Richman DP, Rowin J, Sanders DB, Siddiqi Z, Soloway A, Wolfe GI, Wulf C, Drachman DB, Traynor BJ. BMJ Open. 2020 Sep 18;10(9):e037909. doi: 10.1136/bmjopen-2020-037909.

Monoclonal Antibody-Based Therapies for Myasthenia Gravis. Alabbad S, AlGaeed M, Sikorski P, Kaminski HJ. BioDrugs. 2020 Oct;34(5):557-566. doi: 10.1007/s40259-020-00443-w.

Single-cell repertoire tracing identifies rituximab refractory B cells during myasthenia gravis relapses. Jiang, R., M. L. Fichtner, K. B. Hoehn, P. Stathopoulos, R.J. Nowak, S. H. Kleinstein, K. C. O’Connor. JCI Insight. 2020 Jul 23;5(14):e136471. doi: 10.1172/jci.insight.136471.

Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Meffre E, O'Connor KC. Immunol Rev. 2019 Nov;292(1):90-101. doi: 10.1111/imr.12821. Epub 2019 Nov 12.

Pediatric contributions and lessons learned from the NEPTUNE cohort study. Modi ZJ, Zhai Y, Yee J, Desmond H, Hao W, Sampson MG, Sethna CB, Wang CS, Gipson DS, Trachtman H, Kretzler M; NEPTUNE investigators. Pediatr Nephrol. 2024 Jan 18. doi: 10.1007/s00467-023-06256-7. Epub ahead of print. PMID: 38233720

Primary glomerular diseases are a group of conditions that affect kidney function by attacking the glomeruli, which are kidney structures responsible for filtering the blood and removing waste in urine. NEPTUNE is a rare disease network that focuses on patients with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. The NEPTUNE longitudinal cohort study collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data from patients of all ages to develop a molecular classification for these disorders.

In this review, researchers provide a snapshot of pediatric patients and lessons learned from the NEPTUNE cohort study. The team summarizes key observations and describes the development of the NEPTUNE Match program, which provides individualized guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile of each patient.

Authors note that NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages, including children and adolescents.

Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today. Trachtman H, Desmond H, Williams AL, Mariani LH, Eddy S, Ju W, Barisoni L, Ascani HK, Uhlmann WR, Spino C, Holzman LB, Sedor JR, Gadegbeku C, Subramanian L, Lienczewski CC, Manieri T, Roberts SJ, Gipson DS, Kretzler M; NEPTUNE investigators. Kidney Int. 2024 Feb;105(2):218-230. doi: 10.1016/j.kint.2023.11.018. PMID: 38245210

Glomerular diseases are a group of rare conditions that affect kidney function by attacking the glomeruli, causing problems with the kidney’s filtering system. These diseases include focal segmental glomerular sclerosis (FSGS), minimal change disease, and membranous nephropathy. Glomerular diseases are associated with debilitating symptoms like swelling, protein leakage in urine, and loss of kidney function, sometimes leading to kidney failure. Despite the same diagnosis, response to treatment and disease progression can vary considerably, suggesting differences in disease biology. Few treatments are available, and the efficacy of approved treatments and potential drugs in clinical trials are diminished when patients with differing disease biology are grouped together. 

In this paper, researchers describe the design and implementation of the NEPTUNE Match study. This study is designed to effectively communicate individualized reports to participants and their physicians about the molecular features of their disease state, informing decisions about the suitability of available clinical trials and treatment options. This also paves the way for patients with different rare diseases who share a common disease pathway to be treated using existing, approved drugs.

Authors note that NEPTUNE Match represents the first application of precision medicine in nephrology with the aim of developing targeted therapies and providing the right medication for each patient with primary glomerular disease.

An atlas of healthy and injured cell states and niches in the human kidney. Lake BB, Menon R, Winfree S, Hu Q, Ferreira RM, Kalhor K, Barwinska D, Otto EA, Ferkowicz M, Diep D, Plongthongkum N, Knoten A, Urata S, Mariani LH, Naik AS, Eddy S, Zhang B, Wu Y, Salamon D, Williams JC, Wang X, Balderrama KS, Hoover PJ, Murray E, Marshall JL, Noel T, Vijayan A, Hartman A, Chen F, Waikar SS, Rosas SE, Wilson FP, Palevsky PM, Kiryluk K, Sedor JR, Toto RD, Parikh CR, Kim EH, Satija R, Greka A, Macosko EZ, Kharchenko PV, Gaut JP, Hodgin JB; KPMP Consortium; Eadon MT, Dagher PC, El-Achkar TM, Zhang K, Kretzler M, Jain S. Nature. 2023 Jul;619(7970):585-594. doi: 10.1038/s41586-023-05769-3. Epub 2023 Jul 19. PMID: 37468583; PMCID: PMC10356613

Kidney diseases are characterized by damage and loss of function in the kidneys. Due to the complexity of the kidney, models that accurately represent human kidney structures and function have been difficult to develop. Without these models, the development of new drugs to treat or prevent kidney disease has been limited.

In this study, a nationwide research team aimed to create the most comprehensive atlas of the human kidney. The team used multiple techniques—including single-cell assays, single-nucleus assays, and spatial imaging technologies—to analyze both healthy reference kidneys and diseased kidneys.

The resulting Kidney Tissue Atlas includes maps of 51 main kidney cell types from rare and novel cell populations, 28 kidney cellular states representing injury or disease, a repository of raw gene data, and interactive 3D models of cells and microenvironment relationships. By allowing the comparison of healthy kidney cells to those injured by kidney disease, data from the new atlas will help investigators understand the factors that contribute to the progression of kidney disease and kidney failure or recovery from injury.

An integrated organoid omics map extends modeling potential of kidney disease. Lassé M, El Saghir J, Berthier CC, Eddy S, Fischer M, Laufer SD, Kylies D, Hutzfeldt A, Bonin LL, Dumoulin B, Menon R, Vega-Warner V, Eichinger F, Alakwaa F, Fermin D, Billing AM, Minakawa A, McCown PJ, Rose MP, Godfrey B, Meister E, Wiech T, Noriega M, Chrysopoulou M, Brandts P, Ju W, Reinhard L, Hoxha E, Grahammer F, Lindenmeyer MT, Huber TB, Schlüter H, Thiel S, Mariani LH, Puelles VG, Braun F, Kretzler M, Demir F, Harder JL, Rinschen MM. Nat Commun. 2023 Aug 14;14(1):4903. doi: 10.1038/s41467-023-39740-7. PMID: 37580326; PMCID: PMC10425428

Kidney diseases are characterized by damage and loss of function in the kidneys. Kidney organoids are a promising model to study kidney disease. However, a better understanding of these models and their relevance to disease is critical to advance their use. 

In this study, researchers created an integrated kidney organoid omics map, capturing the complexity of human kidney disease. The team combined omics data from organoid disease models and other preclinical models with data from humans with disease, showing that both inflammation and fibrosis can be rapidly triggered in organoids even in the absence of immune cells.

The new map will enable modeling of more complex kidney disease, driving better outcomes for patients. Authors suggest that other kidney disease researchers can integrate these datasets with their own to improve and refine the creation of organoids relevant to kidney disease.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis. Mariani LH, Eddy S, AlAkwaa FM, McCown PJ, Harder JL, Nair V, Eichinger F, Martini S, Ademola AD, Boima V, Reich HN, El Saghir J, Godfrey B, Ju W, Tanner EC, Vega-Warner V, Wys NL, Adler SG, Appel GB, Athavale A, Atkinson MA, Bagnasco SM, Barisoni L, Brown E, Cattran DC, Coppock GM, Dell KM, Derebail VK, Fervenza FC, Fornoni A, Gadegbeku CA, Gibson KL, Greenbaum LA, Hingorani SR, Hladunewich MA, Hodgin JB, Hogan MC, Holzman LB, Jefferson JA, Kaskel FJ, Kopp JB, Lafayette RA, Lemley KV, Lieske JC, Lin JJ, Menon R, Meyers KE, Nachman PH, Nast CC, O'Shaughnessy MM, Otto EA, Reidy KJ, Sambandam KK, Sedor JR, Sethna CB, Singer P, Srivastava T, Tran CL, Tuttle KR, Vento SM, Wang CS, Ojo AO, Adu D, Gipson DS, Trachtman H, Kretzler M. Kidney Int. 2023 Mar;103(3):565-579. doi: 10.1016/j.kint.2022.10.023. Epub 2022 Nov 25. PMID: 36442540

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are kidney disorders characterized by damaged glomeruli, which are kidney structures responsible for filtering the blood and removing waste in urine. Although these disorders have similar clinical presentations and treatment approaches, response to therapies and risk of progression to kidney failure varies widely among patients. Personalized treatments are currently unavailable due to limited understanding of disease mechanisms and lack of tools to identify biologically relevant subgroups.

In this study, researchers investigated the molecular pathways that are shared by subgroups of patients with MCD and FSGS. First, the team identified groups of patients with shared molecular signatures from kidney biopsy tissue. Next, they identified the pathways from these signatures that could be evaluated in individual patients using noninvasive markers measured in the urine.

Authors note that these markers of disease mechanisms may enable targeted therapeutic interventions for subgroups of patients with MCD and FSGS.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease. Gupta Y, Friedman DJ, McNulty MT, Khan A, Lane B, Wang C, Ke J, Jin G, Wooden B, Knob AL, Lim TY, Appel GB, Huggins K, Liu L, Mitrotti A, Stangl MC, Bomback A, Westland R, Bodria M, Marasa M, Shang N, Cohen DJ, Crew RJ, Morello W, Canetta P, Radhakrishnan J, Martino J, Liu Q, Chung WK, Espinoza A, Luo Y, Wei WQ, Feng Q, Weng C, Fang Y, Kullo IJ, Naderian M, Limdi N, Irvin MR, Tiwari H, Mohan S, Rao M, Dube GK, Chaudhary NS, Gutiérrez OM, Judd SE, Cushman M, Lange LA, Lange EM, Bivona DL, Verbitsky M, Winkler CA, Kopp JB, Santoriello D, Batal I, Pinheiro SVB, Oliveira EA, Simoes E Silva AC, Pisani I, Fiaccadori E, Lin F, Gesualdo L, Amoroso A, Ghiggeri GM, D'Agati VD, Magistroni R, Kenny EE, Loos RJF, Montini G, Hildebrandt F, Paul DS, Petrovski S, Goldstein DB, Kretzler M, Gbadegesin R, Gharavi AG, Kiryluk K, Sampson MG, Pollak MR, Sanna-Cherchi S. Nat Commun. 2023 Nov 30;14(1):7836. doi: 10.1038/s41467-023-43020-9. PMID: 38036523; PMCID: PMC10689833

Focal segmental glomerulosclerosis (FSGS) is a kidney disorder characterized by scarring of a limited number of glomeruli (kidney structures responsible for filtering the blood and removing waste in urine). African Americans have a significantly higher risk of developing chronic kidney disease, especially FSGS, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity.

In this study, researchers investigated the role of the APOL1 p.N264K variant in G2-associated FSGS and chronic kidney disease. The team compared the frequency of this variant in patients with FSGS and those without kidney disease, conducting a comprehensive analysis to explore its impact.

Results show a strong protective effect of the variant against APOL1-related FSGS and chronic kidney disease, countering the toxic effect of the G2 allele. Authors note that this allows APOL1 high-risk individuals to be reclassified as non-high-risk if they carry the variant.

The Significance of Hematuria in Podocytopathies. Marchel D, Trachtman H, Larkina M, Helmuth M, Lai Yee JY, Fermin D, Bomback AS, Canetta PA, Gipson DS, Mottl AK, Parekh RS, Saha MK, Sampson MG, Lafayette RA, Mariani LH; Nephrotic Syndrome Study Network (NEPTUNE); Cure Glomerulonephropathy (CureGN). Clin J Am Soc Nephrol. 2023 Sep 21. doi: 10.2215/CJN.0000000000000309. Epub ahead of print. PMID: 37733352

Podocytopathies are kidney diseases in which injury to podocytes (cells that form the last barrier of the kidney filtration unit) cause nephrotic syndrome. Hematuria (blood in urine) is common in podocytopathies. However, the significance and predictive value of hematuria in these diseases is not well understood.

In this study, researchers describe the prevalence and association between hematuria and kidney-related outcomes in podocytopathies. The team assessed hematuria in urine samples from 1,516 adults and children with podocytopathies.

Results show that hematuria was prevalent among participants and associated with worse kidney-related outcomes, including progressive loss of kidney function and lower rates of proteinuria remission.

A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis. McNulty MT, Fermin D, Eichinger F, Jang D, Kretzler M, Burtt NP, Pollak MR, Flannick J, Weins A, Friedman DJ; Nephrotic Syndrome Study Network (NEPTUNE), Sampson MG. Kidney Int. 2022 Jul;102(1):136-148. doi: 10.1016/j.kint.2021.10.041. Epub 2021 Dec 18.

ADAR regulates APOL1 via A-to-I RNA editing by inhibition of MDA5 activation in a paradoxical biological circuit. Riella CV, McNulty M, Ribas GT, Tattersfield CF, Perez-Gill C, Eichinger F, Kelly J, Chun J, Subramanian B, Guizelini D; Nephrotic Syndrome Study Network (NEPTUNE), Alper SL, Pollak MR, Sampson MG, Friedman DJ. Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2210150119. doi: 10.1073/pnas.2210150119. Epub 2022 Oct 25. PMID: 36282916; PMCID: PMC9636950.

APOL1-associated kidney disease may be caused by two copies of risk variants in the APOL1 gene. However, the disease only occurs in some individuals who carry these variants. Kidney-damaging levels of APOL1 production may be activated by viral illnesses or other environmental factors. In this study, researchers investigated the factors that lead to APOL1-associated kidney disease. The team found that a type of RNA modification called adenosine-to-inosine (A-to-I) editing—carried out by adenosine deaminase acting on RNA (ADAR)—suppressed APOL1 gene expression mediated by inflammatory pathways. Without ADAR editing, APOL1’s messenger RNA triggered inflammation. These findings suggest that ADAR counters rapid production of APOL1 during acute inflammation. Authors note that this important process could impact the severity of APOL1-associated kidney disease.

Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases. Mitrofanova A, Fontanella A, Tolerico M, Mallela S, Molina David J, Zuo Y, Boulina M, Kim JJ, Santos J, Ge M, Sloan A, Issa W, Gurumani M, Pressly J, Ito M, Kretzler M, Eddy S, Nelson R, Merscher S, Burke G, Fornoni A. J Am Soc Nephrol. 2022 Dec;33(12):2153-2173. doi: 10.1681/ASN.2021101286. Epub 2022 Oct 5. PMID: 36198430; PMCID: PMC9731637

Glomerular diseases are a group of conditions that affect kidney function by attacking the glomeruli, which are kidney structures responsible for filtering the blood and removing waste in urine. Diabetic kidney disease (DKD) and Alport syndrome are two types of glomerular diseases. Stimulator of IFN genes (STING)—a signaling molecule—is a crucial regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. Under conditions of obesity, kidney fibrosis, and acute kidney injury, this signaling pathway regulates inflammation and energy homeostasis. However, the role of the STING pathway in glomerular diseases is unclear. In this study, researchers investigated whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome. The team used several mouse models, including diabetic and Alport, to assess the role of the STING signaling pathway in kidney failure. Results suggest that activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Authors state that targeting STING may offer a therapeutic option to treat glomerular diseases and prevent their development or progression.

Assessment of Fibrinogen-like 2 (FGL2) in Human Chronic Kidney Disease through Transcriptomics Data Analysis. Denicolò S, Nair V, Leierer J, Rudnicki M, Kretzler M, Mayer G, Ju W, Perco P. Biomolecules. 2022 Dec 31;13(1):89. doi: 10.3390/biom13010089. PMID: 36671474; PMCID: PMC9855364

Chronic kidney disease (CKD) is a condition characterized by a loss of kidney function over time. Although there can be many causes of CKD, most involve fibrosis, where tissue in the kidneys becomes hardened and scarred. Methods to treat fibrosis in CKD remain limited. However, fibrinogen-like 2 (FGL2)—a protein involved in immune and T-cell function—was recently found to be associated with fibrosis in a mouse model of kidney damage, making it a potential therapeutic target in CKD. In this study, researchers investigated the association of FGL2 gene expression with kidney function and disease outcomes in patients with CKD and healthy controls. The team also assessed the localization of FGL2 in kidney biopsies of CKD patients and identified regulators of FGL2 gene expression in renal tissue. Results show that renal FGL2 mRNA expression was elevated in patients with CKD. Higher FGL2 levels were also associated with fibrosis and worse outcomes. Authors note that these findings suggest an important role of FGL2 in human CKD and fibrosis.

Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes. Wang CS, Troost JP, Wang Y, Greenbaum LA, Gibson K, Trachtman H, Srivastava T, Reidy K, Kaskel F, Sethna CB, Meyers K, Dell KM, Tran CL, Hingorani S, Lemley KV, Lin JJ, Gipson DS. Wang CS, Troost JP, Wang Y, Greenbaum LA, Gibson K, Trachtman H, Srivastava T, Reidy K, Kaskel F, Sethna CB, Meyers K, Dell KM, Tran CL, Hingorani S, Lemley KV, Lin JJ, Gipson DS. Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes. Pediatr Nephrol. 2022 Jul;37(7):1585-1595. doi: 10.1007/s00467-021-05176-8. Epub 2021 Nov 18. PMID: 34796395.

Nephrotic syndrome is a group of symptoms caused by a variety of disorders that damage the kidneys. Pediatric patients with nephrotic syndrome take medications long-term with significant toxicity and complex regimens. However, not much is known about medication adherence in this population. In this study, researchers aimed to understand the determinants of medication adherence and its potential impact on clinical outcomes in childhood nephrotic syndrome. A total of 225 adolescent patients under 19 years old and caregivers completed medication adherence surveys during a 3-year follow-up. Researchers assessed the relationship between adherence and subsequent steroid response, as well as healthcare utilization. Results show that medication nonadherence is common in pediatric nephrotic syndrome. Nonadherence did not show statistically significant associations with steroid resistance or frequency of hospitalizations and emergency room visits. Authors state that more research is needed on the use of surveys in the clinical setting to identify at-risk patients, as well as ways to support families over time.

Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. Watts AJB, Keller KH, Lerner G, Rosales I, Collins AB, Sekulic M, Waikar SS, Chandraker A, Riella LV, Alexander MP, Troost JP, Chen J, Fermin D, Yee JL, Sampson MG, Beck LH Jr, Henderson JM, Greka A, Rennke HG, Weins A. J Am Soc Nephrol. 2022 Jan;33(1):238-252. doi: 10.1681/ASN.2021060794. Epub 2021 Nov 3. PMID: 34732507; PMCID: PMC8763186.

Implications of Sphingolipid Metabolites in Kidney Diseases. Mallela SK, Merscher S, Fornoni A. Mallela SK, Merscher S, Fornoni A. Implications of Sphingolipid Metabolites in Kidney Diseases. Int J Mol Sci. 2022 Apr 11;23(8):4244. doi: 10.3390/ijms23084244. PMID: 35457062; PMCID: PMC9025012.

Sphingolipids are lipids with complex structures that act as bioactive signaling molecules. They are involved in several cellular processes, including cell survival, proliferation, migration, and apoptosis. Abnormalities in the levels of sphingolipids are associated with several human diseases, including kidney diseases. Studies demonstrate that sphingolipids play an important role in maintaining proper renal function. Sphingolipids can alter the glomerular filtration barrier (GFB, a membrane that prevents the passage of the majority of proteins into the urine) by affecting the functioning of podocytes, which are key cellular components of the GFB. In this review paper, researchers summarize studies of the regulation of sphingolipid signaling in kidney diseases, especially in glomerular and tubulointerstitial diseases. Authors also discuss the potential to target sphingolipid pathways in developing therapeutics for the treatment of renal diseases

Kidney Biopsy Features Most Predictive of Clinical Outcomes in the Spectrum of Minimal Change Disease and Focal Segmental Glomerulosclerosis. Zee J, Liu Q, Smith AR, Hodgin JB, Rosenberg A, Gillespie BW, Holzman LB, Barisoni L, Mariani LH; Nephrotic Syndrome Study Network (NEPTUNE); NEPTUNE Members. J Am Soc Nephrol. 2022 Jul;33(7):1411-1426. doi: 10.1681/ASN.2021101396. Epub 2022 May 17. PMID: 35581011; PMCID: PMC9257823.

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are kidney disorders that damage the glomeruli, which are tiny blood vessels in the kidneys. Historically, classification of these disorders has been based on limited features of the glomeruli. Because disease course and treatment response are diverse among patients, a more detailed evaluation of kidney tissue features is needed. In this study, researchers aimed to identify the most important descriptors of clinical outcomes in the Nephrotic Syndrome Study Network (NEPTUNE). The team used supervised machine learning methods—with pathology data collected through applying the NEPTUNE Digital Pathology Scoring System to NEPTUNE kidney biopsies—to evaluate predictors of disease progression, complete proteinuria remission, and treatment response. Researchers found that the most predictive descriptors of outcomes included conventional and novel histologic and ultrastructural features from both glomerular and tubulointerstitial renal compartments. Authors note that standardized reporting of these descriptors could help inform predictions for clinical outcomes.

Molecular Characterization of Membranous Nephropathy. Sealfon R, Mariani L, Avila-Casado C, Nair V, Menon R, Funk J, Wong A, Lerner G, Hayashi N, Troyanskaya O, Kretzler M, Beck LH Jr. J Am Soc Nephrol. 2022 Jun;33(6):1208-1221. doi: 10.1681/ASN.2021060784. Epub 2022 Apr 27.

Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome. Hodgin JB, Mariani LH, Zee J, Liu Q, Smith AR, Eddy S, Hartman J, Hamidi H, Gaut JP, Palmer MB, Nast CC, Chang A, Hewitt S, Gillespie BW, Kretzler M, Holzman LB, Barisoni L; Nephrotic Syndrome Study Network (NEPTUNE). Am J Kidney Dis. 2022 Jun;79(6):807-819.e1. doi: 10.1053/j.ajkd.2021.10.004. Epub 2021 Dec 3.

Classification systems for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) need improvement. In research published in the American Journal of Kidney Diseases involving 221 patients with MCD and FSGS in the Nephrotic Syndrome Study Network (NEPTUNE), investigators applied the NEPTUNE Digital Pathology Scoring System to generate scores for 37 glomerular descriptors. Three clusters were identified. Clusters Y and Z had higher probabilities of proteinuria remission, lower risks of disease progression, and lower kidney function loss over time compared with X. Cluster X had 1,920 differentially expressed genes compared with Y+Z, which reflected activation of pathways of immune response and inflammation. Six descriptors correlated with clinical outcomes and gene expression.

T-cell receptor diversity in minimal change disease in the NEPTUNE study. Liu S, Bush WS, Miskimen K, Gonzalez-Vicente A, Bailey JNC, Konidari I, McCauley JL, Sedor JR, O'Toole JF, Crawford DC. Pediatr Nephrol. 2022 Aug 9. doi: 10.1007/s00467-022-05696-x. Epub ahead of print. PMID: 35943576

Minimal change disease (MCD) is one of the most common causes of childhood idiopathic nephrotic syndrome, which is characterized by severe proteinuria (high levels of protein in the urine) and edema (swelling of body parts). For most patients with MCD, proteinuria is rapidly reversible with corticosteroid therapy. However, relapses are common, and repeated courses of immunosuppressive therapy often lead to many adverse events in children. In this study, researchers explored the role of abnormal T-cell function in these outcomes. The team sequenced T-cell receptors with clinical data and blood samples from patients collected by the Nephrotic Syndrome Study Network (NEPTUNE). To assess the differences between active disease and remission states, researchers calculated several T-cell receptor diversity metrics. Resulting data do not support an obvious role of the adaptive immune system T-cells in the development of MCD. However, given the study’s limited sample size, authors note that further investigation is warranted.

Targeting Endoplasmic Reticulum for Novel Therapeutics and Monitoring in Acute Kidney Injury. Li C, Krothapalli S, Chen YM. Nephron. 2022 Sep 16:1-4. doi: 10.1159/000526050. Epub ahead of print. PMID: 36116429

Acute kidney injury (AKI) is a sudden episode of kidney failure or damage that occurs over a few hours or days. New evidence shows that endoplasmic reticulum (ER) stress—which occurs when proteins are not properly folded—is involved in AKI. However, there are currently no treatments for AKI, including ER-targeted therapies. In this study, researchers aimed to explore the role of ER in AKI. The team outlined several therapeutic chemicals that can target the ER for treatment of AKI. Additionally, researchers identified several potential ER stress biomarkers for early diagnosis and treatment response monitoring in patients with AKI. Based on this evidence, authors conclude that ER plays a critical role in the pathogenesis and progression of AKI. Authors also emphasize an urgent need to develop ER-targeted therapeutics and discover more ER stress biomarkers at the early stage of AKI.

A rare autosomal dominant variant in Regulator of Calcineurin Type 1 (RCAN1) gene confers enhanced calcineurin activity and may cause FSGS. Lane BM, Murray S, Benson K, Bierzynska A, Chryst-Stangl M, Wang L, Wu G, Cavalleri G, Doyle B, Fennelly N, Dorman A, Conlon S, Vega-Warner V, Fermin D, Vijayan P, Qureshi MA, Shril S, Barua M, Hildebrandt F, Pollak M, Howell D, Sampson MG, Saleem M, Conlon PJ, Spurney R, Gbadegesin R. J Am Soc Nephrol. 2021 Apr 16;32(7):1682–95. doi: 10.1681/ASN.2020081234. Epub ahead of print. PMID: 33863784; PMCID: PMC8425665. 

AMPK mediates regulation of glomerular volume and podocyte survival. Banu K, Lin Q, Basgen JM, Planoutene M, Wei C, Reghuvaran AC, Tian X, Shi H, Garzon F, Garzia A, Chun N, Cumpelik A, Santeusanio AD, Zhang W, Das B, Salem F, Li L, Ishibe S, Cantley LG, Kaufman L, Lemley KV, Ni Z, He JC, Murphy B, Menon MC. JCI Insight. 2021 Oct 8;6(19):e150004. doi: 10.1172/jci.insight.150004. PMID: 34473647; PMCID: PMC8525649.

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis. Zee J, McNulty MT, Hodgin JB, Zhdanova O, Hingorani S, Jefferson JA, Gibson KL, Trachtman H, Fornoni A, Dell KM, Reich HN, Bagnasco S, Greenbaum LA, Lafayette RA, Gipson DS, Brown E, Kretzler M, Appel G, Sambandam KK, Tuttle KR, Chen D, Atkinson MA, Hogan MC, Kaskel FJ, Meyers KE, O'Toole J, Srivastava T, Sethna CB, Hladunewich MA, Lin JJ, Nast CC, Derebail VK, Patel J, Vento S, Holzman LB, Athavale AM, Adler SG, Lemley KV, Lieske JC, Hogan JJ, Gadegbeku CA, Fervenza FC, Wang CS, Matar RB, Singer P, Kopp JB, Barisoni L, Sampson MG. Pediatr Nephrol. 2021 Sep;36(9):2747-57. doi: 10.1007/s00467-021-04990-4. Epub 2021 Mar 1. PMID: 33646395; PMCID: PMC8524347. 

Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice. Miyata KN, Lo CS, Zhao S, Liao MC, Pang Y, Chang SY, Peng J, Kretzler M, Filep JG, Ingelfinger JR, Zhang SL, Chan JSD. Clin Sci (Lond). 2021;135:943-61. doi: 10.1042/CS20210094. PMID: 33822013; PMCID: PMC8131957. 

Association of Obesity with Cardiovascular Risk Factors and Kidney Disease Outcomes in Primary Proteinuric Glomerulopathies. Shah PP, Brady TM, Meyers KEC, O'Shaughnessy MM, Gibson KL, Srivastava T, Zee J, Cattran D, Tuttle KR, Gadegbeku C, Glenn D, Derebail V, Smith A, Wang CS, Gillespie BW, Bitzer M, Sethna CB. Nephron. 2021;145:245-55. doi: 10.1159/000513869. PMID: 33677435; PMCID: PMC8102330.

Development and evaluation of deep learning-based segmentation of histologic structures in the kidney cortex with multiple histologic stains. Jayapandian CP, Chen Y, Janowczyk AR, Palmer MB, Cassol CA, Sekulic M, Hodgin JB, Zee J, Hewitt SM, O'Toole J, Toro P, Sedor JR, Barisoni L, Madabhushi A, Nephrotic Syndrome Study Network (NEPTUNE). Kidney Int. 2021;99:86-101. doi: 10.1016/j.kint.2020.07.044. PMID: 32835732; PMCID: PMC8414393.

Follistatin-Like-1 (FSTL1) Is a Fibroblast-Derived Growth Factor That Contributes to Progression of Chronic Kidney Disease. Maksimowski NA, Song X, Bae EH, Reich H, John R, Pei Y, Scholey JW, Nephrotic Syndrome Study Network Neptune. Int J Mol Sci. 2021;22:9513. doi: 10.3390/ijms22179513. PMID: 34502419; PMCID: PMC8431028.

Researchers seeking to better understand the progression of chronic kidney disease studied an animal model of progressive nephropathy, performing microarray analysis of the kidneys of Col4a3-/- mice at 4 and 7 weeks of age. Their goal was to identify new genes that may play a role in tubule-interstitial injury. Authors found that the gene Follistatin-like-1 (FSTL1) contributes to fibrosis (scarring), inflammation, and apoptosis (cell death) in the kidney. Their findings suggest that FSTL1 may be a new treatment target in chronic kidney disease.

Kidney Injury Molecule-1 Urinary Excretion and Tissue Expression Levels and the Prediction of Glomerular Disease Outcomes. Wu Q, Troost JP, Dai T, Nast C, Eddy S, Wei B, Wang Y, Gipson DS, Dell KM, Gipson KL, Kretzler M, Adler S. Glomerular Dis. 2021;1:45-59. doi: 10.1159/000513166. PMID: 34337593; PMCID: PMC8323791.

Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome. Trachtman H, Laskowski J, Lee C, Renner B, Feemster A, Parikh S, Panzer SE, Zhong W, Cravedi P, Cantarelli C, Kulik L, You Z, Satchell S, Rovin B, Liu F, Kalled SL, Holers VM, Jalal D, Thurman JM. Am J Physiol Renal Physiol. 2021 Oct 1;321(4):F505-F516. doi: 10.1152/ajprenal.00041.2021. Epub 2021 Aug 30. PMID: 34459222; PMCID: PMC8560405.

Nephrotic syndrome disease activity is proportional to its associated hypercoagulopathy. Waller AP, Troost JP, Parikh SV, Wolfgang KJ, Rovin BH, Nieman MT, Smoyer WE, Kretzler M, Kerlin BA; NEPTUNE Investigators. Thromb Res. 2021 May;201:50-59. doi: 10.1016/j.thromres.2021.02.007. Epub 2021 Feb 16. PMID: 33636573; PMCID: PMC8096658.

This study aimed to establish the relationship between disease severity and hypercoagulopathy (an increased tendency of the blood to form clots) in human nephrotic syndrome. Consistent with previous animal model observations, researchers found that hypercoagulopathy was proportional to conventional measures of nephrotic syndrome activity, and that it improved significantly with partial or complete disease remission. Study authors expect these data will inform studies designed to stratify thrombotic risk for patients with nephrotic syndrome.

Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis (FSGS): A NEPTUNE study. Maksimowski NA, Scholey JW, Williams VR, Nephrotic Syndrome Study Network (NEPTUNE). PLoS ONE 16(6): e0252758. https://doi.org/10.1371/journal.pone.0252758

In this study, gene expression data and clinical variables gathered from 111 subjects with FSGS were analyzed to compare relationships between angiotensin-converting enzyme 2 (ACE2) expression, clinical variables, and pathology in males and females. Researchers concluded sex is an important determinant of ACE2 expression in the tubules of the kidney and the tissues that surround them. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.

The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis. Moran SM, Scott J, Clarkson MR, Conlon N, Dunne J, Griffin MD, Griffin TP, Groarke E, Holian J, Judge C, Wyse J, McLoughlin K, O'Hara PV, Little MA, Kretzler M; Nephrotic Syndrome Study Network (NEPTUNE). J Am Soc Nephrol. 2021 Nov;32(11):2920-2932. doi: 10.1681/ASN.2021030382. Epub 2021 Sep 13. PMID: 34518279; PMCID: PMC8806104.

ANCA-associated vasculitis (AAV) is a group of diseases characterized by the destruction and inflammation of small vessels. Up to 70% of patients with AAV develop glomerulonephritis (GN), which is inflammation of the tiny filters in the kidneys (glomeruli). Of those, 26% progress to end-stage kidney disease. Researchers are seeking to develop a noninvasive biomarker of active renal vasculitis in order to reliably detect disease before irreversible organ damage occurs. In this study, researchers assessed urinary soluble CD16 (usCD16) as a potential biomarker. They established a reference range and assessed its use in several patient populations. They found that usCD16 is elevated in patients with renal vasculitis. They also found that false positive results can be corrected with urine protein normalization.

Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures. Latt KZ, Heymann J, Jessee JH, Rosenberg AZ, Berthier CC, Arazi A, Eddy S, Yoshida T, Zhao Y, Chen V, Nelson GW, Cam M, Kumar P, Mehta M, Kelly MC, Kretzler M; Nephrotic Syndrome Study Network (NEPTUNE); Accelerating Medicines Partnership in Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Ray PE, Moxey-Mims M, Gorman GH, Lechner BL, Regunathan-Shenk R, Raj DS, Susztak K, Winkler CA, Kopp JB. Kidney Int Rep. 2021 Nov 25;7(2):289-304. doi: 10.1016/j.ekir.2021.11.005. PMID: 35155868; PMCID: PMC8821042.

Assessment of a computerized quantitative quality control tool for kidney whole slide image biopsies. Chen Y, Zee J, Smith A, Jayapandian C, Hodgin J, Howell D, Palmer M, Thomas D, Cassol C, Farris AB 3rd, Perkinson K, Madabhushi A, Barisoni L, Janowczyk A. J Pathol. 2020;253:268-78. doi: 10.1002/path.5590. PMID: 33197281; PMCID: PMC8392148. 

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Jia X, Yamamura T, Gbadegesin R, McNulty MT, Song K, Nagano C, Hitomi Y, Lee D, Aiba Y, Khor SS, Ueno K, Kawai Y, Nagasaki M, Noiri E, Horinouchi T, Kaito H, Hamada R, Okamoto T, Kamei K, Kaku Y, Fujimaru R, Tanaka R, Shima Y; Research Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in Japan, Baek J, Kang HG, Ha IS, Han KH, Yang EM; Korean Consortium of Hereditary Renal Diseases in Children, Abeyagunawardena A, Lane B, Chryst-Stangl M, Esezobor C, Solarin A; Midwest Pediatric Nephrology Consortium (Genetics of Nephrotic Syndrome Study Group), Dossier C, Deschênes G; NEPHROVIR, Vivarelli M, Debiec H, Ishikura K, Matsuo M, Nozu K, Ronco P, Cheong HI, Sampson MG, Tokunaga K, Iijima K. Kidney Int. 2020;98:1308-22. doi: 10.1016/j.kint.2020.05.029. PMID: 32554042; PMCID: PMC8101291. 

Digital pathology and computational image analysis in nephropathology. Barisoni L, Lafata KJ, Hewitt SM, Madabhushi A, Balis UGJ. Nat Rev Nephrol. 2020 Nov;16(11):669-685. doi: 10.1038/s41581-020-0321-6. Epub 2020 Aug 26.

Dynamic treatment regimens in small n, sequential, multiple assignment, randomized trials: An application in focal segmental glomerulosclerosis. Chao YC, Trachtman H, Gipson DS, Spino C, Braun TM, Kidwell KM. Contemp Clin Trials. 2020;92:105989. doi: 10.1016/j.cct.2020.105989. PMID: 32200006; PMCID: PMC8173713. 

Incorporating longitudinal biomarkers for dynamic risk prediction in the era of big data: A pseudo-observation approach. Zhao L, Murray S, Mariani LH, Ju W. Stat Med. 2020 Nov 20;39(26):3685-3699. doi: 10.1002/sim.8687. Epub 2020 Jul 27.

JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy. Tao J, Mariani L, Eddy S, Maecker H, Kambham N, Mehta K, Hartman J, Wang W, Kretzler M, Lafayette RA. Clin J Am Soc Nephrol. 2020 Jul 1;15(7):973-982. doi: 10.2215/CJN.11010919. Epub 2020 Apr 30. PMID: 32354727; PMCID: PMC7341773. 

IgA nephropathy, also known as Berger’s disease, is a kidney disorder that occurs when IgA (immunoglobulin A), a protein that helps the body fight infections, settles in the kidneys. Deposits of IgA may cause the kidneys to leak blood and sometimes protein in the urine and lead to progressive kidney fibrosis or scarring. Researchers seeking to understand and target the mechanisms behind the disease undertook detailed investigations of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway, which is believed to be an important mediator of kidney disease. They compared 77 patients with IgA nephropathy with 45 healthy subjects. Researchers found that JAK-STAT signaling was activated in patients with IgA nephropathy compared with controls, finding altered responses in peripheral immune cells and increased message and activated proteins in the kidney function. Authors say their findings strongly support that the JAK-STAT signaling pathway is altered in diverse kidney diseases, in ways that are likely unique to each disease.

Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental Glomerulosclerosis. Merchant ML, Barati MT, Caster DJ, Hata JL, Hobeika L, Coventry S, Brier ME, Wilkey DW, Li M, Rood IM, Deegens JK, Wetzels JF, Larsen CP, Troost JP, Hodgin JB, Mariani LH, Kretzler M, Klein JB, McLeish KR. J Am Soc Nephrol. 2020;31(8):1883-1904. doi: 10.1681/ASN.2019070696. PMID: 32561683; PMCID: PMC7460901. 

Role of direct oral anticoagulants in patients with kidney disease. Derebail VK, Rheault MN, Kerlin BA. Derebail VK, Rheault MN, Kerlin BA. Role of direct oral anticoagulants in patients with kidney disease. Kidney Int. 2020 Apr;97(4):664-675. doi: 10.1016/j.kint.2019.11.027. Epub 2019 Dec 24. PMID: 32107019; PMCID: PMC7093256.

Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker. Menon R, Otto EA, Hoover P, Eddy S, Mariani L, Godfrey B, Berthier CC, Eichinger F, Subramanian L, Harder J, Ju W, Nair V, Larkina M, Naik AS, Luo J, Jain S, Sealfon R, Troyanskaya O, Hacohen N, Hodgin JB, Kretzler M, Kpmp KPMP; Nephrotic Syndrome Study Network (NEPTUNE). JCI Insight. 2020;5:e133267. doi: 10.1172/jci.insight.133267. PMID: 32107344; PMCID: PMC7213795. 

Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes. Royal V, Zee J, Liu Q, Avila-Casado C, Smith AR, Liu G, Mariani LH, Hewitt S, Holzman LB, Gillespie BW, Hodgin JB, Barisoni L. J Am Soc Nephrol. 2020;31:841-54. doi: 10.1681/ASN.2019080825. PMID: 32086276; PMCID: PMC7191920. 

Urinary CD80 Discriminates Among Glomerular Disease Types and Reflects Disease Activity. Gonzalez Guerrico AM, Lieske J, Klee G, Kumar S, Lopez-Baez V, Wright AM, Bobart S, Shevell D, Maldonado M, Troost JP, Hogan MC; Nephrotic Syndrome Study Network Consortium (NEPTUNE). Kidney Int Rep. 2020;5:2021-31. doi: 10.1016/j.ekir.2020.08.001. PMID: 33163723; PMCID: PMC7609973. 

Disruption of the exocyst induces podocyte loss and dysfunction. Nihalani D, Solanki AK, Arif E, Srivastava P, Rahman B, Zuo X, Dang Y, Fogelgren B, Fermin D, Gillies CE, Sampson MG, Lipschutz JH. J Biol Chem. 2019 Jun 28;294(26):10104-10119. doi: 10.1074/jbc.RA119.008362. Epub 2019 May 9.

Endoplasmic reticulum stress and monogenic kidney diseases in precision nephrology. Park SJ, Kim Y, Chen YM. Pediatr Nephrol. 2019 Sep;34(9):1493-1500. doi: 10.1007/s00467-018-4031-2. Epub 2018 Aug 11.

Identification of dicarbonyl and L-xylulose reductase as a therapeutic target in human chronic kidney disease. Perco P, Ju W, Kerschbaum J, Leierer J, Menon R, Zhu C, Kretzler M, Mayer G, Rudnicki M; Nephrotic Syndrome Study Network (NEPTUNE). JCI Insight. 2019;4:e128120. doi: 10.1172/jci.insight.128120. PMID: 31217356; PMCID: PMC6629103.

Identification of glomerular and podocyte-specific genes and pathways activated by sera of patients with focal segmental glomerulosclerosis. Otalora L, Chavez E, Watford D, Tueros L, Correa M, Nair V, Ruiz P, Wahl P, Eddy S, Martini S, Kretzler M, Burke GW 3rd, Fornoni A, Merscher S. PLoS One. 2019;14:e0222948. doi: 10.1371/journal.pone.0222948. PMID: 31581251; PMCID: PMC6776339. 

Methods for Assessing Longitudinal Biomarkers of Time-to-Event Outcomes in CKD: A Simulation Study. Liu Q, Smith AR, Mariani LH, Nair V, Zee J. Clin J Am Soc Nephrol. 2019;14:1315-23, doi: 10.2215/CJN.00450119. PMID: 31416887; PMCID: PMC6730514.

Organoid single cell profiling identifies a transcriptional signature of glomerular disease. Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, O'Connor C, Luo J, Nair V, Cebrian C, Spence JR, Bitzer M, Troyanskaya OG, Hodgin JB, Wiggins RC, Freedman BS, Kretzler M; European Renal cDNA Bank (ERCB); Nephrotic Syndrome Study Network (NEPTUNE). JCI Insight. 2019;4:e122697. doi: 10.1172/jci.insight.122697. PMID: 30626756;PMCID: PMC6485369.

Plasma Zonulin Levels in Childhood Nephrotic Syndrome. Trachtman H, Gipson DS, Lemley KV, Troost JP, Faul C, Morrison DJ, Vento SM, Ahn DH, Goldberg JD. Front Pediatr. 2019;7:197. doi:10.3389/fped.2019.00197. PMID: 31157195;PMCID: PMC6532587.

Renal SGLT mRNA expression in human health and disease: a study in two cohorts. Srinivasan Sridhar V, Ambinathan JPN, Kretzler M, Pyle LL, Bjornstad P, Eddy S, Cherney DZ, Reich HN; European Renal cDNA Bank (ERCB); Nephrotic Syndrome Study Network (NEPTUNE). Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1224-F1230. doi: 10.1152/ajprenal.00370.2019. Epub 2019 Sep 23. PMID: 31545924; PMCID: PMC6879935.

Text Messaging for Disease Monitoring in Childhood Nephrotic Syndrome. Wang CS, Troost JP, Greenbaum LA, Srivastava T, Reidy K, Gibson K, Trachtman H, Piette JD, Sethna CB, Meyers K, Dell KM, Tran CL, Vento S, Kallem K, Herreshoff E, Hingorani S, Lemley K, Oh G, Brown E, Lin JJ, Kaskel F, Gipson DS. Kidney Int Rep. 2019;4:1066-74. doi:10.1016/j.ekir.2019.04.026. PMID: 31440697; PMCID: PMC6698307.

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network. Troost JP, Waldo A, Carlozzi NE, Murphy S, Modersitzski F, Trachtman H, Nachman PH, Reidy KJ, Selewski DT, Herreshoff EG, Srivastava T, Gibson KL, Derebail VK, Lin JJ, Hingorani S, Fornoni A, Fervenza FC, Sambandam K, Athavale AM, Kopp JB, Reich HN, Adler SG, Greenbaum LA, Dell KM, Appel G, Wang C, Sedor J, Kaskel FJ, Lafayette RA, Atkinson MA,Lieske JC, Sethna CB, Kretzler M, Hladunewich MA, Lemley KV, Brown E,Meyers KE,Gadegbeku CA, Holzman LB,Jefferson JA, Tuttle KR, Singer P, Hogan MC, Cattran DC, Barisoni L, Gipson DS, Nephrotic Syndrome Study Network. Clin Kidney J. 2019;13:597-606. doi: 10.1093/ckj/sfz092. PMID:32905199; PMCID: PMC7467600.

Using All Longitudinal Data to Define Time to Specified Percentages of Estimated GFR Decline: A Simulation Study. Zee J, Mansfield S, Mariani LH, Gillespie BW. Am J Kidney Dis. 2018;73:82-9. doi: 10.1053/j.ajkd.2018.07.009.PMID: 30249420;PMCID: PMC6309673.

Using PROMIS® to create clinically meaningful profiles of nephrotic syndrome patients. Troost JP, Gipson DS, Carlozzi NE, Reeve BB, Nachman PH, Gbadegesin R, Wang J, Modersitzki F, Massengill S, Mahan JD, Liu Y, Trachtman H, Herreshoff EG, DeWalt DA, Selewski DT. Health Psychol. 2019;38: 410-21. doi: 10.1037/hea0000679. PMID: 31045424; PMCID: PMC6499490. 

An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis. Troost JP, Trachtman H, Nachman PH, Kretzler M, Spino C, Komers R, Tuller S, Perumal K, Massengill SF, Kamil ES, Oh G, Selewski DT, Gipson P, Gipson DS. Clin J Am Soc Nephrol. 2017;13:414-21. doi: 10.2215/CJN.04780517. PMID: 29167190; PMCID: PMC5967666. 

An eQTL Landscape of Kidney Tissue in Human Nephrotic Syndrome. Gillies CE, Putler R, Menon R, Otto E, Yasutake K, Nair V, Hoover P, Lieb D, Li S, Eddy S, Fermin D, McNulty MT; Nephrotic Syndrome Study Network (NEPTUNE), Hacohen N, Kiryluk K, Kretzler M, Wen X, Sampson MG. Am J Hum Genet. 2018;103:232-44. doi: 10.1016/j.ajhg.2018.07.004. PMID: 30057032; PMCID: PMC6081280. 

Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment. Hommos MS, Zeng C, Liu Z, Troost JP, Rosenberg AZ, Palmer M, Kremers WK, Cornell LD, Fervenza FC, Barisoni L, Rule AD. Kidney Int. 2017;93:1175-85. doi: 10.1016/j.kint.2017.09.028. PMID: 29273332; PMCID: PMC5911429. 

Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Mariani LH, Martini S, Barisoni L, Canetta PA, Troost JP, Hodgin JB, Palmer M, Rosenberg AZ, Lemley KV, Chien HP, Zee J, Smith A, Appel GB, Trachtman H, Hewitt SM, Kretzler M, Bagnasco SM. Nephrol Dial Transplant. 2017;33:1-9. doi: 10.1093/ndt/gfw443; PMID: 28339906; PMCID: PMC5837529. 

JAK-STAT signaling is activated in the kidney and peripheral blood cells of patients with focal segmental glomerulosclerosis. Tao J, Mariani L, Eddy S, Maecker H, Kambham N, Mehta K, Hartman J, Wang W, Kretzler M, Lafayette RA. Kidney Int. 2018;94:795-808. doi: 10.1016/j.kint.2018.05.022. PMID: 30093081; PMCID: PMC6744284. 

Metabolic pathways and immunometabolism in rare kidney diseases. Grayson PC, Eddy S, Taroni JN, Lightfoot YL, Mariani L, Parikh H, Lindenmeyer MT, Ju W, Greene CS, Godfrey B, Cohen CD, Krischer J, Kretzler M, Merkel PA; Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network. Ann Rheum Dis. 2018;77:1226-33. doi: 10.1136/annrheumdis-2017-212935. PMID: 29724730; PMCID: PMC6045442. 

Renal matrix Gla protein expression increases progressively with CKD and predicts renal outcome. Miyata KN, Nast CC, Dai T, Dukkipati R, LaPage JA, Troost JP, Schurgers LJ, Kretzler M, Adler SG. Exp Mol Pathol. 2018;105:120-9. doi: 10.1016/j.yexmp.2018.07.001. PMID: 29981754; PMCID: PMC6167754. 

Reproducibility and Feasibility of Strategies for Morphologic Assessment of Renal Biopsies Using the Nephrotic Syndrome Study Network Digital Pathology Scoring System. Zee J, Hodgin JB, Mariani LH, Gaut JP, Palmer MB, Bagnasco SM, Rosenberg AZ, Hewitt SM, Holzman LB, Gillespie BW, Barisoni L. Arch Pathol Lab Med.2018;142:613-25. doi: 10.5858/arpa.2017-0181-OA. PMID: 29457738;PMCID: PMC5946059.

Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome. Debiec H, Dossier C, Letouzé E, Gillies CE, Vivarelli M, Putler RK, Ars E, Jacqz-Aigrain E, Elie V, Colucci M, Debette S, Amouyel P, Elalaoui SC, Sefiani A, Dubois V, Simon T, Kretzler M, Ballarin J, Emma F, Sampson MG, Deschênes G, Ronco P. J Am Soc Nephrol. 2018;29:2000-13. doi: 10.1681/ASN.2017111185. PMID: 29903748; PMCID: PMC6050942. 

APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts. Ng DK, Robertson CC, Woroniecki RP, Limou S, Gillies CE, Reidy KJ, Winkler CA, Hingorani S, Gibson KL, Hjorten R, Sethna CB, Kopp JB, Moxey-Mims M, Furth SL, Warady BA, Kretzler M, Sedor JR, Kaskel FJ, Sampson MG. Nephrol Dial Transplant. 2016;32:983-90. doi: 10.1093/ndt/gfw061. PMID: 27190333; PMCID: PMC5837652.

Blood Pressure and Visit-to-Visit Blood Pressure Variability Among Individuals With Primary Proteinuric Glomerulopathies. Sethna CB, Meyers KEC, Mariani LH, Psoter KJ, Gadegbeku CA, Gibson KL, Srivastava T, Kretzler M, Brady TM. Hypertension. 2017;70:315-23. doi: 10.1161/HYPERTENSIONAHA.117.09475. PMID: 28652469; PMCID: PMC5518633.

Digital pathology imaging as a novel platform for standardization and globalization of quantitative nephropathology. Barisoni L, Gimpel C, Kain R, Laurinavicius A, Bueno G, Caihong Z, Zhihong L, Schaefer F, Kretzler M, Holzman LB, Hewitt SM. Clin Kidney J. 2017;10:176-87. doi: 10.1093/ckj/sfw129; PMID: 28584625; PMCID: PMC5455257.

Digital pathology in nephrology clinical trials, research, and pathology practice. Barisoni L, Hodgin JB. Curr Opin Nephrol Hypertens. 2017 Nov;26(6):450-459. doi: 10.1097/MNH.0000000000000360. PMID: 28858910; PMCID: PMC5955389.

Evaluating Mendelian nephrotic syndrome genes for evidence for risk alleles or oligogenicity that explain heritability. Crawford BD, Gillies CE, Robertson CC, Kretzler M, Otto EA, Vega-Warner V, Sampson MG. Pediatr Neph. 2017;32:467-476. doi:10.1007/s00467-016-3513-3. PMID: 27766458; PMCID: PMC5483602. 

Learning to live with nephrotic syndrome: experiences of adult patients and parents of children with nephrotic syndrome. Beanlands H, Maione M, Poulton C, Herreshoff E, Hladunewich MA, Hailperin M, Modes MM, An L, Nunes JW, Trachtman H, Nachman P, Gipson DS. Nephrol Dial Transplant. 2017;32 (suppl_1): i98-i105. doi: 10.1093/ndt/gfw344. PMID: 28391342; PMCID: PMC5837224. 

Provider perspectives on treatment decision-making in nephrotic syndrome. Hladunewich MA, Beanlands H, Herreshoff E, Troost JP, Maione M, Trachtman H, Poulton C, Nachman P, Modes MM, Hailperin M, Pitter R, Gipson DS. Nephrol Dial Transplant. 2017;32 (suppl_1): i106-i14. doi: 10.1093/ndt/gfw309. PMID: 28391336; PMCID: PMC5837354. 

Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor Dependent. Sharma R, Waller AP, Agrawal S, Wolfgang KJ, Luu H, Shahzad K, Isermann B, Smoyer WE, Nieman MT, Kerlin BA. J Am Soc Nephrol. 2017 Sep;28(9):2618-2630. doi: 10.1681/ASN.2016070789. Epub 2017 Apr 19.

Complete Remission in the Nephrotic Syndrome Study Network. Gipson DS, Troost JP, Lafayette RA, Hladunewich MA, Trachtman H, Gadegbeku CA, Sedor JR, Holzman LB, Moxey-Mims MM, Perumal K, Kaskel FJ, Nelson PJ, Tuttle KR, Bagnasco SM, Hogan MC, Dell KM, Appel GB, Lieske JC, Ilori TO, Sethna CB, Fervenza FC, Hogan SL, Nachman PH, Rosenberg AZ, Greenbaum LA, Meyers KE, Hewitt SM, Choi MJ, Kopp JB, Zhdanova O, Hodgin JB, Johnstone DB, Adler SG, Avila-Casado C, Neu AM, Hingorani SR, Lemley KV, Nast CC, Brady TM, Barisoni-Thomas L, Fornoni A, Jennette JC, Cattran DC, Palmer MB, Gibson KL, Reich HN, Mokrzycki MH, Sambandam KK, Zilleruelo GE, Licht C, Sampson MG, Song P, Mariani LH, Kretzler M. Clin J Am Soc Nephrol. 2016;11:81-9. doi: 10.2215/CJN.02560315; PMID: 26656320; PMCID: PMC4702222.

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects. Sampson MG, Robertson CC, Martini S, Mariani LH, Lemley KV, Gillies CE, Otto EA, Kopp JB, Randolph A, Vega-Warner V, Eichinger F, Nair V, Gipson DS, Cattran DC, Johnstone DB, O'Toole JF, Bagnasco SM, Song PX, Barisoni L, Troost JP, Kretzler M, Sedor JR; Nephrotic Syndrome Study Network. J Am Soc Nephrol. 2016;27:814-23. doi: 10.1681/ASN.2014111131. PMID: 26150607; PMCID: PMC4769193. 

Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury. Pedigo CE, Ducasa GM, Leclercq F, Sloan A, Mitrofanova A, Hashmi T, Molina-David J, Ge M, Lassenius MI, Forsblom C, Lehto M, Groop PH, Kretzler M, Eddy S, Martini S, Reich H, Wahl P, Ghiggeri G, Faul C, Burke GW 3rd, Kretz O, Huber TB, Mendez AJ, Merscher S, Fornoni A. J Clin Invest. 2016;126:3336-50. doi:10.1172/JCI85939. PMID: 27482889; PMCID: PMC5004940. 

Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies: A Longitudinal Cohort Study Using Generalized Estimating Equations. Lemley KV, Bagnasco SM, Nast CC, Barisoni L, Conway CM, Hewitt SM, Song PX. PLoS One. 2016; 11: e0157148. doi: 10.1371/journal.pone.0157148. PMID: 27285824; PMCID: PMC4902229. 

Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images. Barisoni L, Troost JP, Nast C, Bagnasco S, Avila-Casado C, Hodgin J, Palmer M, Rosenberg A, Gasim A, Liensziewski C, Merlino L, Chien HP, Chang A, Meehan SM, Gaut J, Song P, Holzman L, Gibson D, Kretzler M, Gillespie BW, Hewitt SM. Mod Pathol. 2016;29:671-84. doi: 10.1038/modpathol.2016.58. PMID: 27102348; PMCID: PMC5515468. 

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies. Rosenberg AZ, Palmer M, Merlino L, Troost JP, Gasim A, Bagnasco S, Avila-Casado C, Johnstone D, Hodgin JB, Conway C, Gillespie BW, Nast CC, Barisoni L, Hewitt SM. PLoS One. 2016 Jun 16;11(6):e0156441. doi: 10.1371/journal.pone.0156441. PMID: 27310011; PMCID: PMC4911144.

The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Haas ME, Levenson AE, Sun X, Liao WH, Rutkowski JM, de Ferranti SD, Schumacher VA, Scherer PE, Salant DJ, Biddinger SB. Circulation. 2016 Jul 5;134(1):61-72. doi: 10.1161/CIRCULATIONAHA.115.020912. PMID: 27358438; PMCID: PMC5345853. 

The relatively poor correlation between random and 24-hour urine protein excretion in patients with biopsy-proven glomerular diseases. Hogan MC, Reich HN, Nelson PJ, Adler SG, Cattran DC, Appel GB, Gipson DS, Kretzler M, Troost JP, Lieske JC. Kidney Int. 2016;90:1080-9. doi: 10.1016/j.kint.2016.06.020. PMID: 27528553; PMCID: PMC5065749. 

Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case Cohort. Sampson MG, Gillies CE, Robertson CC, Crawford B, Vega-Warner V, Otto EA, Kretzler M, Kang HM. J Am Soc Nephrol. 2016;27:1970-83. doi: 10.1681/ASN.2015050504. PMID: 26534921; PMCID: PMC4926977. 

tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine. Gillies CE, Otto EA, Vega-Warner V, Robertson CC, Sanna-Cherchi S, Gharavi A, Crawford B, Bhimma R, Winkler C; Nephrotic Syndrome Study Network (NEPTUNE); C-PROBE Investigator Group of the Michigan Kidney Translational Core Center, Kang HM, Sampson MG. BMC Bioinformatics. 2016;17:233. doi: 10.1186/s12859-016-1108-4. PMID: 27287006; PMCID: PMC4902911. 

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Spinale JM, Mariani LH, Kapoor S, Zhang J, Weyant R, Song PX, Wong HN, Troost JP, Gadegbeku CA, Gipson DS, Kretzler M, Nihalani D, Holzman LB; Nephrotic Syndrome Study Network. Kidney Int. 2015;87:564–74. doi:10.1038/ki.2014.346. PMID: 25354239;PMCID:PMC4344842.

Defining nephrotic syndrome from an integrative genomics perspective. Sampson MG, Hodgin JB, Kretzler M. Pediatr Nephrol. 2015;30:51-63; quiz 59. doi: 10.1007/s00467-014-2857-9. PMID: 24890338;PMCID: PMC4241380.

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome. Kerlin BA, Waller AP, Sharma R, Chanley MA, Nieman MT, Smoyer WE. J Am Soc Nephrol. 2015 Dec;26(12):3009-19. doi: 10.1681/ASN.2014111097. Epub 2015 Apr 8.

Morphology in the Digital Age: Integrating High-Resolution Description of Structural Alterations With Phenotypes and Genotypes. Nast CC, Lemley KV, Hodgin JB, Bagnasco S, Avila-Casado C, Hewitt SM, Barisoni L. Semin Nephrol. 2015;35:266-78. doi: 10.1016/j.semnephrol.2015.04.006. PMID: 26215864;PMCID: PMC4764351.

Strategy and rationale for urine collection protocols employed in the NEPTUNE study. Hogan MC, Lieske JC, Lienczewski CC, Nesbitt LL, Wickman LT, Heyer CM, Harris PC, Ward CJ, Sundsbak JL, Manganelli L, Ju W, Kopp JB, Nelson PJ, Adler SG, Reich HN, Holzmann LB, Kretzler M, Bitzer M. MBC Nephrol. 2015;16:190. doi: 10.1186/s12882-015-0185-3; PMID: 26577187; PMCID: PMC4650313.

Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Ju W, Nair V, Smith S, Zhu L, Shedden K, Song PXK, Mariani LH, Eichinger FH, Berthier CC, Randolph A, Lai JY, Zhou Y, Hawkins JJ, Bitzer M, Sampson MG, Thier M, Solier C, Duran-Pacheco GC, Duchateau-Nguyen G, Essioux L, Schott B, Formentini I, Magnone MC, Bobadilla M, Cohen CD, Bagnasco SM, Barisoni L, Lv J, Zhang H, Wang HY, Brosius FC, Gadegbeku CA, Kretzler M; ERCB, C-PROBE, NEPTUNE, and PKU-IgAN Consortium. Sci Transl Med.7(316), 2015,doi: 10.1126/scitranslmed.aac7071.PMID:26631632; PMCID: PMC4861144.

Glomerular diseases: emerging tests and therapies for IgAnephropathy. Canetta PA, Kiryluk K, Appel GB. Clin J Am Soc Nephrol. 2014;9:617-25; doi: 10.2215/CJN.07260713. PMID: 24071652; PMCID: PMC3944769.

Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten. Moeller S, Canetta PA, Taylor AK, Arguelles-Grande C, Snyder H, Green PH, Kiryluk K, Alaedini A. PLoS One. 2014 Apr 14;9(4):e94677. doi: 10.1371/journal.pone.0094677. PMID: 24732864; PMCID: PMC3986214.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multi-disciplinary approach. Gadegbeku CA, Gipson DS, Holzman LB, Ojo AO, Song PX, Barisoni L, Sampson MG, Kopp JB, Lemley KV, Nelson PJ, Lienczewski CC, Adler SG, Appel GB, Cattran DC, Choi MJ, Contreras G, Dell KM, Fervenza FC, Gibson KL, Greenbaum LA, Hernandez JD, Hewitt SM, Hingorani SR, Hladunewich M, Hogan MC, Hogan SL, Kaskel FJ, Lieske JC, Meyers KE, Nachman PH, Nast CC, Neu AM, Reich HN, Sedor JR, Sethna CB, Trachtman H, Tuttle KR, Zhdanova O, Zilleruelo GE, Kretzler M. Kidney Int. 2013;83:749-56. doi:10.1038/ki.2012.428. PMID: 23325076; PMCID: PMC3612359.

Digital pathology evaluation in the multicenter Nephrotic Syndrome Study Network (NEPTUNE). Barisoni L, Nast CC, Jennette JC, Hodgin JB, Herzenberg AM, Lemley KV, Conway CM, Kopp JB, Kretzler M, Lienczewski C, Avila-Casado C, Bagnasco S, Sethi S, Tomaszewski J, Gasim AH, Hewitt SM. Clin J Am Soc Nephrol. 2013 Aug;8(8):1449-59. doi: 10.2215/CJN.08370812. Epub 2013 Feb 7. PMID: 23393107; PMCID: PMC3731905.

Genes, Exomes, Genomes, Copy Number: What is Their Future in Pediatric Renal Disease. Sampson MG, Jüppner H. Curr Pediatr Rep. 2013;1:52-9. doi:10.1007/s40124-012-0001-5. PMID: 27642543; PMCID: PMC5022771. 

Amino acid ratio combinations as biomarkers for discriminating patients with pyruvate dehydrogenase complex deficiency from other inborn errors of metabolism. Verma A, Lehman AN, Gokcan H, Cropcho L, Black D, Dobrowolski SF, Vockley J, Bedoyan JK. Mol Genet Genomic Med. 2023 Sep 8:e2283. doi: 10.1002/mgg3.2283. Epub ahead of print. PMID: 37688338.

Clinical, biochemical and molecular characterization of 12 patients with pyruvate carboxylase deficiency treated with triheptanoin. Duque Lasio LM, Leshinski AC, Ducich NH, Flore LA, Lehman A, Shur N, Jayakar PB, Hainline BE, Basinger AA, Wilson WG, Diaz GA, Erbe RW, Koeberl DD, Vockley J, Bedoyan JK. Mol. Genet. Metab. 139: doi: 10.1016/j.ymgme.2023.107605. PMID: 37207470.

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators. Neurology. 2023 Jul 18;101(3):e238-e252. doi: 10.1212/WNL.0000000000207402. Epub 2023 Jun 2.

Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants. Vogel GF, Mozer-Glassberg Y, Landau YE, Schlieben LD, Prokisch H, Feichtinger RG, Mayr JA, Brennenstuhl H, Schröter J, Pechlaner A, Alkuraya FS, Baker JJ, Barcia G, Baric I, Braverman N, Burnyte B, Christodoulou J, Ciara E, Coman D, Das AM, Darin N, Della Marina A, Distelmaier F, Eklund EA, Ersoy M, Fang W, Gaignard P, Ganetzky RD, Gonzales E, Howard C, Hughes J, Konstantopoulou V, Kose M, Kerr M, Khan A, Lenz D, McFarland R, Margolis MG, Morrison K, Müller T, Murayama K, Nicastro E, Pennisi A, Peters H, Piekutowska-Abramczuk D, Rötig A, Santer R, Scaglia F, Schiff M, Shagrani M, Sharrard M, Soler-Alfonso C, Staufner C, Storey I, Stormon M, Taylor RW, Thorburn DR, Teles EL, Wang JS, Weghuber D, Wortmann S. Genet Med. 2023 Jun;25(6):100314. doi: 10.1016/j.gim.2022.09.015. Epub 2022 Oct 29.

Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations. Solis EM, Good LB, Vázquez RG, Patnaik S, Hernandez-Reynoso AG, Ma Q, Angulo G, Dobariya A, Cogan SF, Pancrazio JJ, Pascual JM, Jakkamsetti V. bioRxiv. 2023 Aug 20:2023.06.05.543611. doi: 10.1101/2023.06.05.543611. Preprint.

Progressive external ophthalmoplegia. Hirano M, Pitceathly RDS. Handb Clin Neurol. 2023;194:9-21. doi: 10.1016/B978-0-12-821751-1.00018-X.

Single-cell multi-omics of mitochondrial DNA disorders reveals dynamics of purifying selection across human immune cells. Lareau CA, Dubois SM, Buquicchio FA, Hsieh YH, Garg K, Kautz P, Nitsch L, Praktiknjo SD, Maschmeyer P, Verboon JM, Gutierrez JC, Yin Y, Fiskin E, Luo W, Mimitou EP, Muus C, Malhotra R, Parikh S, Fleming MD, Oevermann L, Schulte J, Eckert C, Kundaje A, Smibert P, Vardhana SA, Satpathy AT, Regev A, Sankaran VG, Agarwal S, Ludwig LS. Nat Genet. 2023 Jul;55(7):1198-1209. doi: 10.1038/s41588-023-01433-8. Epub 2023 Jun 29. PMID: 37386249

Mitochondrial diseases are multisystemic, genetic disorders involving dysfunction of the mitochondria (specialized cell structures that produce energy), which affects cellular metabolism. Diverse mitochondrial DNA (mtDNA) mutations are associated with diverse phenotypes (observable characteristics), suggesting that metabolic vulnerabilities may be specific to organ and cell types.

In this study, researchers developed a multi-omics approach to investigate the properties of mitochondrial genetics. In single cells derived from six patients with mitochondrial diseases, the team quantified deletions in mtDNA alongside cell state features.

Results reveal the dynamics of pathogenic (disease-causing) mtDNA heteroplasmy (multiple variants within a cell) in individual blood and immune cells. Authors note that these findings demonstrate the power of single-cell multi-omics to reveal fundamental properties of mitochondrial genetics.

The evolution of the mitochondrial disease diagnostic odyssey. Thompson JLP, Karaa A, Pham H, Yeske P, Krischer J, Xiao Y, Long Y, Kramer A, Dimmock D, Holbert A, Gorski C, Engelstad KM, Buchsbaum R, Rosales XQ, Hirano M. Orphanet J Rare Dis. 2023 Jun 22;18(1):157. doi: 10.1186/s13023-023-02754-x.

A homozygous splice variant in ATP5PO, disrupts mitochondrial complex V function and causes Leigh syndrome in two unrelated families. Ganapathi M, Friocourt G, Gueguen N, Friederich MW, Le Gac G, Okur V, Loaëc N, Ludwig T, Ka C, Tanji K, Marcorelles P, Theodorou E, Lignelli-Dipple A, Voisset C, Walker MA, Briere LC, Bourhis A, Blondel M, LeDuc C, Hagen J, Cooper C, Muraresku C, Ferec C, Garenne A, Lelez-Soquet S, Rogers CA, Shen Y, Strode DK, Bizargity P, Iglesias A, Goldstein A, High FA, Network UD, Sweetser DA, Ganetzky R, Van Hove JLK, Procaccio V, Le Marechal C, Chung WK. J Inherit Metab Dis. 2022 May 27. doi: 10.1002/jimd.12526. Online ahead of print.

Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. Berardo A, Domínguez-González C, Engelstad K, Hirano M. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786.

Community Consensus Guidelines to Support FAIR Data Standards in Clinical Research Studies in Primary Mitochondrial Disease. Karaa A, MacMullen LE, Campbell JC, Christodoulou J, Cohen BH, Klopstock T, Koga Y, Lamperti C, van Maanen R, McFarland R, Parikh S, Rahman S, Scaglia F, Sherman AV, Yeske P, Falk MJ. Adv Genet (Hoboken). 2022 Mar;3(1):2100047. doi: 10.1002/ggn2.202100047. Epub 2021 Dec 19.

Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes. Yang JH, Friederich MW, Ellsworth KA, Frederick A, Foreman E, Malicki D, Dimmock D, Lenberg J, Prasad C, Yu AC, Anthony Rupar C, Hegele RA, Manickam K, Koboldt DC, Crist E, Choi SS, Farhan SMK, Harvey H, Sattar S, Karp N, Wong T, Haas R, Van Hove JLK, Wigby K. Hum Mutat. 2022 Mar;43(3):305-315. doi: 10.1002/humu.24330. Epub 2022 Jan 19.

Implications of mitochondrial DNA mutations in human induced pluripotent stem cells. Carelli V, Hirano M, Enríquez JA, Chinnery PF. Nat Rev Genet. 2022 Feb;23(2):69-70. doi: 10.1038/s41576-021-00430-z.

Mitochondrial DNA maintenance defects: potential therapeutic strategies. Almannai M, El-Hattab AW, Azamian MS, Ali M, Scaglia F. Mol Genet Metab. 2022 Sep-Oct;137(1-2):40-48. doi: 10.1016/j.ymgme.2022.07.003. Epub 2022 Jul 6. PMID: 35914366.

Mitochondrial DNA maintenance defects (MDMDs) are a group of disorders characterized by mitochondrial DNA (mtDNA) depletions and/or multiple deletions. These disorders most often affect the brain, liver, skeletal muscle, peripheral nerves, and gastrointestinal tract. As with other mitochondrial disorders, treatment options for MDMDs are currently limited. Recent progress in MDMD research includes the development of model organisms, improved understanding of their pathophysiology, and a better knowledge of their natural history. This progress has led to an increasing number of preclinical studies, as well as existing and planned clinical trials. In this review paper, researchers discuss current studies and trials, including potential new therapeutic options for MDMDs.

RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. Pernice WM, Eyaid W, Gc JB, Brown ZP, Juanola-Falgarona M, Torres-Torronteras J, Sommerville EW, Hellebrekers DM, Blakely EL, Donaldson A, van de Laar I, Leu CS, Marti R, Frank J, Tanji K, Koolen DA, Rodenburg RJ, Chinnery PF, Smeets HJM, Gorman GS, Bonnen PE, Taylor RW, Hirano M. J Clin Invest. 2022 Jul 1;132(13):e145660. doi: 10.1172/JCI145660. PMID: 35617047; PMCID: PMC9246377.

Mitochondrial DNA depletion/deletions syndromes (MDDS) are a group of inherited disorders in which copies of the DNA (genetic material) within mitochondria (specialized cell structures that produce energy) are severely reduced in number. MDDS are frequently caused by defects in nucleoside and nucleotide metabolism, which is critical for mitochondrial DNA replication. In this study, researchers report five individuals from four families who presented with ptosis (eyelid drooping), ophthalmoplegia (eye muscle weakness), other clinical manifestations, and multiple mitochondrial DNA deletions in muscle. The team identified three variants in the gene RRM1, which affect ribonucleotide reductase protein structure and function, leading to impairment of de novo nucleotide synthesis. These results reveal that both recessive and dominant RRM1 variants cause MDDS. Additionally, these findings demonstrate that elements of the de novo nucleotide synthesis pathway may lead to MDDS.

Simulations of Pathogenic E1α Variants: Allostery and Impact on Pyruvate Dehydrogenase Complex-E1 Structure and Function. Gokcan H, Bedoyan JK, Isayev O. J Chem Inf Model. 2022 Jul 25;62(14):3463-3475. doi: 10.1021/acs.jcim.2c00630. Epub 2022 Jul 7.

Sleep and Breathing Disturbances in Children With Leigh Syndrome: A Comparative Study. Ju Wang JD, Chen M, Zhang C, Parker J, Saneto R, Ramirez JM. Pediatr Neurol. 2022 Nov;136:56-63. doi: 10.1016/j.pediatrneurol.2022.08.006. Epub 2022 Aug 29.

Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function. Ducich NH, Mears JA, Bedoyan JK. J Inherit Metab Dis. 2022 Jan 17. doi: 10.1002/jimd.12477. Online ahead of print.

Time to harmonize mitochondrial syndrome nomenclature and classification: A consensus from the North American Mitochondrial Disease Consortium (NAMDC). Emmanuele V, Ganesh J, Vladutiu G, Haas R, Kerr D, Saneto RP, Cohen BH, Van Hove JLK, Scaglia F, Hoppel C, Rosales XQ, Barca E, Buchsbaum R, Thompson JL, DiMauro S, Hirano M; North American Mitochondrial Disease Consortium (NAMDC). Mol Genet Metab. 2022 Jun;136(2):125-131. doi: 10.1016/j.ymgme.2022.05.001. Epub 2022 May 13.

Homoplasmy of the m. 8993 T>G variant in a patient without MRI findings of Leigh syndrome, ataxia or retinal abnormalities. Saneto RP, Patrick KE, Perez FA. Mitochondrion. 2021 Jul;59:58-62. doi: 10.1016/j.mito.2021.04.010. Epub 2021 Apr 22.

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder. Zolkipli-Cunningham Z, Naviaux JC, Nakayama T, Hirsch CM, Monk JM, Li K, Wang L, Le TP, Meinardi S, Blake DR, Naviaux RK. PLoS One. 2021 Mar 18;16(3):e0248771. doi: 10.1371/journal.pone.0248771. eCollection 2021.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. Hirano M, Carelli V, De Giorgio R, Pironi L, Accarino A, Cenacchi G, D'Alessandro R, Filosto M, Martí R, Nonino F, Pinna AD, Baldin E, Bax BE, Bolletta A, Bolletta R, Boschetti E, Cescon M, D'Angelo R, Dotti MT, Giordano C, Gramegna LL, Levene M, Lodi R, Mandel H, Morelli MC, Musumeci O, Pugliese A, Scarpelli M, Siniscalchi A, Spinazzola A, Tal G, Torres-Torronteras J, Vignatelli L, Zaidman I, Zoller H, Rinaldi R, Zeviani M. J Inherit Metab Dis. 2021 Mar;44(2):376-387. doi: 10.1002/jimd.12300. Epub 2020 Sep 8.

Pathogenic variants in MRPL44 cause infantile cardiomyopathy due to a mitochondrial translation defect. Friederich MW, Geddes GC, Wortmann SB, Punnoose A, Wartchow E, Knight KM, Prokisch H, Creadon-Swindell G, Mayr JA, Van Hove JLK. Mol Genet Metab. 2021 Aug;133(4):362-371. doi: 10.1016/j.ymgme.2021.06.001. Epub 2021 Jun 10.

Regulatory environment for novel therapeutic development in mitochondrial diseases. Hirano M, Berardo A, Barca E, Emmanuele V, Quinzii C, Simpson CV, Engelstad K, Rosales XQ, Thompson JLP. J Inherit Metab Dis. 2021 Mar;44(2):292-300. doi: 10.1002/jimd.12353. Epub 2021 Jan 4.

Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency. Lopez-Gomez C, Sanchez-Quintero MJ, Lee EJ, Kleiner G, Tadesse S, Xie J, Akman HO, Gao G, Hirano M. Ann Neurol. 2021 Oct;90(4):640-652. doi: 10.1002/ana.26185. Epub 2021 Aug 13.

TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation. Murali CN, Soler-Alfonso C, Loomes KM, Shah AA, Monteil D, Padilla CD, Scaglia F, Ganetzky R. Mol Genet Metab. 2021 Feb;132(2):146-153. doi: 10.1016/j.ymgme.2021.01.005. Epub 2021 Jan 14.

A novel acceptor stem variant in mitochondrial tRNA(Tyr) impairs mitochondrial translation and is associated with a severe phenotype. Kripps KA, Friederich MW, Chen T, Larson AA, Mirsky DM, Wang Y, Tanji K, Knight KM, Wong LJ, Van Hove JLK. Mol Genet Metab. 2020 Dec;131(4):398-404. doi: 10.1016/j.ymgme.2020.11.006. Epub 2020 Nov 24.

A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. Karaa A, Haas R, Goldstein A, Vockley J, Cohen BH. J Cachexia Sarcopenia Muscle. 2020 Aug;11(4):909-918. doi: 10.1002/jcsm.12559. Epub 2020 Feb 25.

Clinical Bioinformatics in Precise Diagnosis of Mitochondrial Disease. Shen L, McCormick EM, Muraresku CC, Falk MJ, Gai X. Clin Lab Med. 2020 Jun;40(2):149-161. doi: 10.1016/j.cll.2020.02.002.

Clinical trials in mitochondrial disorders, an update. Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F. Mol Genet Metab. 2020 Sep-Oct;131(1-2):1-13. doi: 10.1016/j.ymgme.2020.10.002. Epub 2020 Oct 6.

Editing the Mitochondrial Genome. Falkenberg M, Hirano M. N Engl J Med. 2020 Oct 8;383(15):1489-1491. doi: 10.1056/NEJMcibr2025332.

Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Martí I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Pérez J, Trifunov S, Cuadras D, Kalko SG, Blázquez-Bermejo C, Cámara Y, Martí R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C. Sci Rep. 2020 Jun 22;10(1):10111. doi: 10.1038/s41598-020-66940-8.

Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6. Berardo A, Emmanuele V, Vargas W, Tanji K, Naini A, Hirano M. J Neurol. 2020 Mar;267(3):823-829. doi: 10.1007/s00415-019-09619-z. Epub 2019 Nov 27.

Mitochondrial diseases in North America: An analysis of the NAMDC Registry. Barca E, Long Y, Cooley V, Schoenaker R, Emmanuele V, DiMauro S, Cohen BH, Karaa A, Vladutiu GD, Haas R, Van Hove JLK, Scaglia F, Parikh S, Bedoyan JK, DeBrosse SD, Gavrilova RH, Saneto RP, Enns GM, Stacpoole PW, Ganesh J, Larson A, Zolkipli-Cunningham Z, Falk MJ, Goldstein AC, Tarnopolsky M, Gropman A, Camp K, Krotoski D, Engelstad K, Rosales XQ, Kriger J, Grier J, Buchsbaum R, Thompson JLP, Hirano M. Neurol Genet. 2020 Mar 2;6(2):e402. doi: 10.1212/NXG.0000000000000402. eCollection 2020 Apr.

Mitochondrial diseases: expanding the diagnosis in the era of genetic testing. Saneto RP. J Transl Genet Genom. 2020;4:384-428. doi: 10.20517/jtgg.2020.40. Epub 2020 Sep 29.

Pathogenic variants in NUBPL result in failure to assemble the matrix arm of complex I and cause a complex leukoencephalopathy with thalamic involvement. Friederich MW, Perez FA, Knight KM, Van Hove RA, Yang SP, Saneto RP, Van Hove JLK. Mol Genet Metab. 2020 Mar;129(3):236-242. doi: 10.1016/j.ymgme.2019.12.013. Epub 2019 Dec 30.

Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation. McCormick EM, Lott MT, Dulik MC, Shen L, Attimonelli M, Vitale O, Karaa A, Bai R, Pineda-Alvarez DE, Singh LN, Stanley CM, Wong S, Bhardwaj A, Merkurjev D, Mao R, Sondheimer N, Zhang S, Procaccio V, Wallace DC, Gai X, Falk MJ. Hum Mutat. 2020 Dec;41(12):2028-2057. doi: 10.1002/humu.24107. Epub 2020 Nov 10.

Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Kripps K, Nakayuenyongsuk W, Shayota BJ, Berquist W, Gomez-Ospina N, Esquivel CO, Concepcion W, Sampson JB, Cristin DJ, Jackson WE, Gilliland S, Pomfret EA, Kueht ML, Pettit RW, Sherif YA, Emrick LT, Elsea SH, Himes R, Hirano M, Van Hove JLK, Scaglia F, Enns GM, Larson AA. Mol Genet Metab. 2020 May;130(1):58-64. doi: 10.1016/j.ymgme.2020.03.001. Epub 2020 Mar 6.

The North American mitochondrial disease registry. Rosales XQ, Thompson JLP, Haas R, Van Hove JLK, Karaa A, Krotoski D, Engelstad K, Buchsbaum R, DiMauro S, Hirano M; North American Mitochondrial Disease Consortium. J Transl Genet Genom. 2020;4:81-90. doi: 10.20517/jtgg.2020.12. Epub 2020 Apr 28.

The mitochondrial DNA variant m.9032T > C in MT-ATP6 encoding p.(Leu169Pro) causes a complex mitochondrial neurological syndrome. Knight KM, Shelkowitz E, Larson AA, Mirsky DM, Wang Y, Chen T, Wong LJ, Friederich MW, Van Hove JLK. Mitochondrion. 2020 Nov;55:8-13. doi: 10.1016/j.mito.2020.08.009. Epub 2020 Sep 12.

Utility of specific amino acid ratios in screening for pyruvate dehydrogenase complex deficiencies and other mitochondrial disorders associated with congenital lactic acidosis and newborn screening prospects. Bedoyan JK, Hage R, Shin HK, Linard S, Ferren E, Ducich N, Wilson K, Lehman A, Schillaci LA, Manickam K, Mori M, Bartholomew D, DeBrosse S, Cohen B, Parikh S, Kerr D. JIMD Rep. 2020 Aug 16;56(1):70-81. doi: 10.1002/jmd2.12153. eCollection 2020 Nov.

A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. Bedoyan JK, Hecht L, Zhang S, Tarrant S, Bergin A, Demirabis D, Wang E, Shin H, Grahame GJ, DeBrosse SD, Hoppel CL, Kerr DS, Berry GT. JIMD Rep. 2019 Jun 17;48(1):26-35.

Advances in primary mitochondrial myopathies. de Barcelos IP, Emmanuele V, Hirano M. Curr Opin Neurol. 2019 Oct;32(5):715-721. doi: 10.1097/WCO.0000000000000743.

Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. Lopez-Gomez C, Hewan H, Sierra C, Akman HO, Sanchez-Quintero MJ, Juanola-Falgarona M, Tadesse S, Tanji K, Konofagou EE, Hirano M. EBioMedicine. 2019 Aug;46:356-367. doi: 10.1016/j.ebiom.2019.07.037. Epub 2019 Aug 2.

Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6. Larson AA, Balasubramaniam S, Christodoulou J, Burrage LC, Marom R, Graham BH, Diaz GA, Glamuzina E, Hauser N, Heese B, Horvath G, Mattman A, van Karnebeek C, Lane Rutledge S, Williamson A, Estrella L, Van Hove JKL, Weisfeld-Adams JD. Mitochondrion. 2019 Jan;44:58-64. doi: 10.1016/j.mito.2018.01.001. Epub 2018 Jan 4.

Cardiomyopathy and altered integrin-actin signaling in Fhl1 mutant female mice. Kubota A, Juanola-Falgarona M, Emmanuele V, Sanchez-Quintero MJ, Kariya S, Sera F, Homma S, Tanji K, Quinzii CM, Hirano M. Hum Mol Genet. 2019 Jan 15;28(2):209-219. doi: 10.1093/hmg/ddy299.

CoQ10 and Aging. Barcelos IP, Haas RH. Biology (Basel). 2019 May 11;8(2):28. doi: 10.3390/biology8020028.

Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Domínguez-González C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodríguez FJ, Donati MA, Kleinsteuber K, Martí I, Martín-Hernández E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Álvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Martí R, Paradas C, Hirano M. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17.

Growth differentiation factor-15 as a biomarker of strength and recovery in survivors of acute respiratory failure. Rosenberg BJ, Hirano M, Quinzii CM, Colantuoni E, Needham DM, Lederer DJ, Baldwin MR. Thorax. 2019 Nov;74(11):1099-1101. doi: 10.1136/thoraxjnl-2019-213621. Epub 2019 Sep 18.

Human aging DNA methylation signatures are conserved but accelerated in cultured fibroblasts. Sturm G, Cardenas A, Bind MA, Horvath S, Wang S, Wang Y, Hägg S, Hirano M, Picard M. Epigenetics. 2019 Oct;14(10):961-976. doi: 10.1080/15592294.2019.1626651. Epub 2019 Jun 12.

Landscape of Germline and Somatic Mitochondrial DNA Mutations in Pediatric Malignancies. Triska P, Kaneva K, Merkurjev D, Sohail N, Falk MJ, Triche TJ Jr, Biegel JA, Gai X. Cancer Res. 2019 Apr 1;79(7):1318-1330. doi: 10.1158/0008-5472.CAN-18-2220. Epub 2019 Feb 1.

Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, Fuiza-Luces C, García García J, Morís G, Olivé M, Miralles F, Díaz-Manera J, Caballero C, Méndez-Ferrer B, Martí R, García Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MÁ, Paradas C. Orphanet J Rare Dis. 2019 May 6;14(1):100. doi: 10.1186/s13023-019-1071-z.

MT-ATP6 mitochondrial disease variants: Phenotypic and biochemical features analysis in 218 published cases and cohort of 14 new cases. Ganetzky RD, Stendel C, McCormick EM, Zolkipli-Cunningham Z, Goldstein AC, Klopstock T, Falk MJ. Hum Mutat. 2019 May;40(5):499-515. doi: 10.1002/humu.23723. Epub 2019 Mar 4.

Mitochondrial Dysfunction in Aging and Diseases of Aging. Haas RH. Biology (Basel). 2019 Jun 17;8(2):48. doi: 10.3390/biology8020048.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy. Gramegna LL, Pisano A, Testa C, Manners DN, D'Angelo R, Boschetti E, Giancola F, Pironi L, Caporali L, Capristo M, Valentino ML, Plazzi G, Casali C, Dotti MT, Cenacchi G, Hirano M, Giordano C, Parchi P, Rinaldi R, De Giorgio R, Lodi R, Carelli V, Tonon C. AJNR Am J Neuroradiol. 2018 Mar;39(3):427-434. doi: 10.3174/ajnr.A5507. Epub 2018 Jan 18.

Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome. Hoff KE, DeBalsi KL, Sanchez-Quintero MJ, Longley MJ, Hirano M, Naini AB, Copeland WC. PLoS One. 2018 Aug 29;13(8):e0203198. doi: 10.1371/journal.pone.0203198. eCollection 2018.

CoQ(10) supplementation rescues nephrotic syndrome through normalization of H(2)S oxidation pathway. Kleiner G, Barca E, Ziosi M, Emmanuele V, Xu Y, Hidalgo-Gutierrez A, Qiao C, Tadesse S, Area-Gomez E, Lopez LC, Quinzii CM. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3708-3722. doi: 10.1016/j.bbadis.2018.09.002. Epub 2018 Sep 6.

Diagnostic odyssey of patients with mitochondrial disease. Johnston Grier, Michio Hirano, Amel Karaa, Emma Shepard, John LP Thompson. Body: Johnston Grier, Michio Hirano, Amel Karaa, Emma Shepard, John L.P. Thompson. Diagnostic odyssey of patients with mitochondrial disease: Results of a survey. Neurol Genet. Apr 2018, 4 (2) e230; DOI: 10.1212/NXG.0000000000000230.

Diagnostic odyssey of patients with mitochondrial disease: Results of a survey. Grier J, Hirano M, Karaa A, Shepard E, Thompson JLP. Neurology Genetics. 2018;4(2):e230. PMID: 29600276, PMCID: PMC5873725.

Emerging therapies for mitochondrial diseases. Hirano M, Emmanuele V, Quinzii CM. Essays Biochem. 2018 Jul 20;62(3):467-481. doi: 10.1042/EBC20170114. Print 2018 Jul 20.

Endocrine Disorders in Primary Mitochondrial Disease. Al-Gadi IS, Haas RH, Falk MJ, Goldstein A, McCormack SE. J Endocr Soc. 2018 Feb 19;2(4):361-373. doi: 10.1210/js.2017-00434. eCollection 2018 Apr 1.

Long-Term Sustained Effect of Liver-Targeted Adeno-Associated Virus Gene Therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy. Torres-Torronteras J, Cabrera-Pérez R, Vila-Julià F, Viscomi C, Cámara Y, Hirano M, Zeviani M, Martí R. Hum Gene Ther. 2018 Jun;29(6):708-718. doi: 10.1089/hum.2017.133. Epub 2018 Feb 26.

MSeqDR mvTool: A mitochondrial DNA Web and API resource for comprehensive variant annotation, universal nomenclature collation, and reference genome conversion. Shen L, Attimonelli M, Bai R, Lott MT, Wallace DC, Falk MJ, Gai X. Hum Mutat. 2018 Jun;39(6):806-810. doi: 10.1002/humu.23422. Epub 2018 Apr 6.

Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease. McCormick EM, Zolkipli-Cunningham Z, Falk MJ. Curr Opin Pediatr. 2018 Dec;30(6):714-724. doi: 10.1097/MOP.0000000000000686.

Mitochondrial disease patient motivations and barriers to participate in clinical trials. Zolkipli-Cunningham Z, Xiao R, Stoddart A, McCormick EM, Holberts A, Burrill N, McCormack S, Williams L, Wang X, Thompson JLP, Falk MJ. PLoS One. 2018 May 17;13(5):e0197513. doi: 10.1371/journal.pone.0197513. eCollection 2018.

Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Karaa A, Haas R, Goldstein A, Vockley J, Weaver WD, Cohen BH. Neurology. 2018 Apr 3;90(14):e1212-e1221. doi: 10.1212/WNL.0000000000005255. Epub 2018 Mar 2.

Retrospective natural history of thymidine kinase 2 deficiency. Garone C, Taylor RW, Nascimento A, Poulton J, Fratter C, Domínguez-González C, Evans JC, Loos M, Isohanni P, Suomalainen A, Ram D, Hughes MI, McFarland R, Barca E, Lopez Gomez C, Jayawant S, Thomas ND, Manzur AY, Kleinsteuber K, Martin MA, Kerr T, Gorman GS, Sommerville EW, Chinnery PF, Hofer M, Karch C, Ralph J, Cámara Y, Madruga-Garrido M, Domínguez-Carral J, Ortez C, Emperador S, Montoya J, Chakrapani A, Kriger JF, Schoenaker R, Levin B, Thompson JLP, Long Y, Rahman S, Donati MA, DiMauro S, Hirano M. J Med Genet. 2018 Aug;55(8):515-521. doi: 10.1136/jmedgenet-2017-105012. Epub 2018 Mar 30.

Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography. Siegmund SE, Grassucci R, Carter SD, Barca E, Farino ZJ, Juanola-Falgarona M, Zhang P, Tanji K, Hirano M, Schon EA, Frank J, Freyberg Z. iScience. 2018 Aug 31;6:83-91. doi: 10.1016/j.isci.2018.07.014. Epub 2018 Jul 20.

USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick EM, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ. Hum Mol Genet. 2018 Oct 1;27(19):3305-3312. doi: 10.1093/hmg/ddy231.

A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder. Garone C, Gurgel-Giannetti J, Sanna-Cherchi S, Krishna S, Naini A, Quinzii CM, Hirano M. J Child Neurol. 2017 Feb;32(2):246-250. doi: 10.1177/0883073816666221. Epub 2016 Sep 28.

Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency. Lopez-Gomez C, Levy RJ, Sanchez-Quintero MJ, Juanola-Falgarona M, Barca E, Garcia-Diaz B, Tadesse S, Garone C, Hirano M. Ann Neurol. 2017 May;81(5):641-652. doi: 10.1002/ana.24922. Epub 2017 May 4.

Disorders of pyruvate metabolism and the tricarboxylic acid cycle. Kerr DS, Bedoyan JK. In Sarafoglou K (ed) Essentials of Pediatric Endocrinology and Metabolism, 2nd Edition, McGraw Hill, 2017.

Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK. Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.

International Workshop: Outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. Consensus recommendations. 16-18 November 2016, Rome, Italy. Mancuso M, McFarland R, Klopstock T, Hirano M; consortium on Trial Readiness in Mitochondrial Myopathies. Neuromuscul Disord. 2017 Dec;27(12):1126-1137. doi: 10.1016/j.nmd.2017.08.006. Epub 2017 Sep 8.

Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Bedoyan JK, Yang SP, Ferdinandusse S, Jack RM, Miron A, Grahame G, DeBrosse SD, Hoppel CL, Kerr DS, Wanders RJA. Mol Genet Metab. 2017 Apr;120(4):342-349. doi: 10.1016/j.ymgme.2017.02.002. Epub 2017 Feb 2.

Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion. Huang X, Bedoyan JK, Demirbas D, Harris DJ, Miron A, Edelheit S, Grahame G, DeBrosse SD, Wong LJ, Hoppel CL, Kerr DS, Anselm I, Berry GT. Mol Genet Metab. 2017 Mar;120(3):213-222. doi: 10.1016/j.ymgme.2016.11.005. Epub 2016 Nov 12.

Advances in purine and pyrimidine metabolism in health and diseases. Hirano M, Peters GJ. Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):495-501. doi: 10.1080/15257770.2016.1218022.

Alpers-Huttenlocher syndrome: the role of a multidisciplinary health care team. Saneto RP. J Multidiscip Healthc. 2016 Jul 26;9:323-33. doi: 10.2147/JMDH.S84900. eCollection 2016.

Attitudes toward prevention of mtDNA-related diseases through oocyte mitochondrial replacement therapy. Engelstad K, Sklerov M, Kriger J, Sanford A, Grier J, Ash D, Egli D, DiMauro S, Thompson JL, Sauer MV, Hirano M. Hum Reprod. 2016 May;31(5):1058-65. doi: 10.1093/humrep/dew033. Epub 2016 Mar 2.

Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. Barca E, Musumeci O, Montagnese F, Marino S, Granata F, Nunnari D, Peverelli L, DiMauro S, Quinzii CM, Toscano A. Clin Genet. 2016 Aug;90(2):156-60. doi: 10.1111/cge.12742. Epub 2016 Feb 16.

FHF1 (FGF12) epileptic encephalopathy. Al-Mehmadi S, Splitt M; For DDD Study group*, Ramesh V, DeBrosse S, Dessoffy K, Xia F, Yang Y, Rosenfeld JA, Cossette P, Michaud JL, Hamdan FF, Campeau PM, Minassian BA; For CENet Study group‡. Neurol Genet. 2016 Oct 28;2(6):e115. doi: 10.1212/NXG.0000000000000115. eCollection 2016 Dec.

Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes. Yamada M, Emmanuele V, Sanchez-Quintero MJ, Sun B, Lallos G, Paull D, Zimmer M, Pagett S, Prosser RW, Sauer MV, Hirano M, Egli D. Cell Stem Cell. 2016 Jun 2;18(6):749-754. doi: 10.1016/j.stem.2016.04.001. Epub 2016 May 19.

Long-Term Restoration of Thymidine Phosphorylase Function and Nucleoside Homeostasis Using Hematopoietic Gene Therapy in a Murine Model of Mitochondrial Neurogastrointestinal Encephalomyopathy. Torres-Torronteras J, Cabrera-Pérez R, Barba I, Costa C, de Luna N, Andreu AL, Barquinero J, Hirano M, Cámara Y, Martí R. Hum Gene Ther. 2016 Sep;27(9):656-67. doi: 10.1089/hum.2015.160. Epub 2016 May 4.

MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease. Shen L, Diroma MA, Gonzalez M, Navarro-Gomez D, Leipzig J, Lott MT, van Oven M, Wallace DC, Muraresku CC, Zolkipli-Cunningham Z, Chinnery PF, Attimonelli M, Zuchner S, Falk MJ, Gai X. Hum Mutat. 2016 Jun;37(6):540-548. doi: 10.1002/humu.22974. Epub 2016 Mar 21.

Mitochondrial Diseases: A Clinical and Molecular History. Pavlakis SG, Hirano M. Pediatr Neurol. 2016 Oct;63:3-5. doi: 10.1016/j.pediatrneurol.2016.05.014. Epub 2016 Jun 2.

Mitochondrial disease patients' perception of dietary supplements' use. Karaa A, Kriger J, Grier J, Holbert A, Thompson JL, Parikh S, Hirano M. Mol Genet Metab. 2016 Sep;119(1-2):100-8. doi: 10.1016/j.ymgme.2016.07.005. Epub 2016 Jul 16.

Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability. Perales-Clemente E, Cook AN, Evans JM, Roellinger S, Secreto F, Emmanuele V, Oglesbee D, Mootha VK, Hirano M, Schon EA, Terzic A, Nelson TJ. EMBO J. 2016 Sep 15;35(18):1979-90. doi: 10.15252/embj.201694892. Epub 2016 Jul 19.

Neuropsychiatric Features in Primary Mitochondrial Disease. Marin SE, Saneto RP. Neurol Clin. 2016 Feb;34(1):247-94. doi: 10.1016/j.ncl.2015.08.011.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Halter JP, Michael W, Schüpbach M, Mandel H, Casali C, Orchard K, Collin M, Valcarcel D, Rovelli A, Filosto M, Dotti MT, Marotta G, Pintos G, Barba P, Accarino A, Ferra C, Illa I, Beguin Y, Bakker JA, Boelens JJ, de Coo IF, Fay K, Sue CM, Nachbaur D, Zoller H, Sobreira C, Pinto Simoes B, Hammans SR, Savage D, Martí R, Chinnery PF, Elhasid R, Gratwohl A, Hirano M. Brain. 2015 Oct;138(Pt 10):2847-58. doi: 10.1093/brain/awv226. Epub 2015 Aug 10.

Clinical and biochemical characterization of four patients with mutations in ECHS1. Ferdinandusse S, Friederich MW, Burlina A, Ruiter J, Coughlin CR, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bennett MJ, Elpeleg O, Van Hove JLK, Wanders RJA. Orphanet J Rare Dis. 2015 Jun 18;10:79.

Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, Anselm I, Cohen BH, Falk MJ, Greene C, Gropman AL, Haas R, Hirano M, Morgan P, Sims K, Tarnopolsky M, Van Hove JL, Wolfe L, DiMauro S. Genet Med. 2015 Sep;17(9):689-701. doi: 10.1038/gim.2014.177. Epub 2014 Dec 11.

Innovative genomic collaboration using the GENESIS (GEM.app) platform. Gonzalez M, Falk MJ, Gai X, Postrel R, Schüle R, Zuchner S. Hum Mutat. 2015 Oct;36(10):950-6. doi: 10.1002/humu.22836. Epub 2015 Aug 12.

Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Falk MJ, Shen L, Gonzalez M, Leipzig J, Lott MT, Stassen AP, Diroma MA, Navarro-Gomez D, Yeske P, Bai R, Boles RG, Brilhante V, Ralph D, DaRe JT, Shelton R, Terry SF, Zhang Z, Copeland WC, van Oven M, Prokisch H, Wallace DC, Attimonelli M, Krotoski D, Zuchner S, Gai X; MSeqDR Consortium Participants; MSeqDR Consortium participants: Sherri Bale, Jirair Bedoyan, Doron Behar, Penelope Bonnen, Lisa Brooks, Claudia Calabrese, Sarah Calvo, Patrick Chinnery, John Christodoulou, Deanna Church,; Rosanna Clima, Bruce H Cohen, Richard G Cotton, IFM de Coo, Olga Derbenevoa, Johan T den Dunnen, David Dimmock, Gregory Enns, Giuseppe Gasparre,; Amy Goldstein, Iris Gonzalez, Katrina Gwinn, Sihoun Hahn, Richard H Haas, Hakon Hakonarson, Michio Hirano, Douglas Kerr, Dong Li, Maria Lvova, Finley Macrae, Donna Maglott, Elizabeth McCormick, Grant Mitchell, Vamsi K Mootha, Yasushi Okazaki,; Aurora Pujol, Melissa Parisi, Juan Carlos Perin, Eric A Pierce, Vincent Procaccio, Shamima Rahman, Honey Reddi, Heidi Rehm, Erin Riggs, Richard Rodenburg, Yaffa Rubinstein, Russell Saneto, Mariangela Santorsola, Curt Scharfe,; Claire Sheldon, Eric A Shoubridge, Domenico Simone, Bert Smeets, Jan A Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong. Mol Genet Metab. 2015 Mar;114(3):388-96. doi: 10.1016/j.ymgme.2014.11.016. Epub 2014 Dec 4.

Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier. Navarro-Gomez D, Leipzig J, Shen L, Lott M, Stassen AP, Wallace DC, Wiggs JL, Falk MJ, van Oven M, Gai X. Bioinformatics. 2015 Apr 15;31(8):1310-2. doi: 10.1093/bioinformatics/btu825. Epub 2014 Dec 12.

ANO10 mutations cause ataxia and coenzyme Q₁₀ deficiency. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. J Neurol. 2014 Nov;261(11):2192-8. doi: 10.1007/s00415-014-7476-7. Epub 2014 Sep 3.

Branching enzyme deficiency: expanding the clinical spectrum. Paradas C, Akman HO, Ionete C, Lau H, Riskind PN, Jones DE, Smith TW, Hirano M, Dimauro S. JAMA Neurol. 2014 Jan;71(1):41-7. doi: 10.1001/jamaneurol.2013.4888.

Clinical presentations of coenzyme q10 deficiency syndrome. Quinzii CM, Emmanuele V, Hirano M. Mol Syndromol. 2014 Jul;5(3-4):141-6. doi: 10.1159/000360490.

Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy. Garcia-Diaz B, Garone C, Barca E, Mojahed H, Gutierrez P, Pizzorno G, Tanji K, Arias-Mendoza F, Quinzii CM, Hirano M. Brain. 2014 May;137(Pt 5):1337-49. doi: 10.1093/brain/awu068. Epub 2014 Apr 10.

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. Garone C, Garcia-Diaz B, Emmanuele V, Lopez LC, Tadesse S, Akman HO, Tanji K, Quinzii CM, Hirano M. EMBO Mol Med. 2014 Aug;6(8):1016-27. doi: 10.15252/emmm.201404092.

Gene therapy using a liver-targeted AAV vector restores nucleoside and nucleotide homeostasis in a murine model of MNGIE. Torres-Torronteras J, Viscomi C, Cabrera-Pérez R, Cámara Y, Di Meo I, Barquinero J, Auricchio A, Pizzorno G, Hirano M, Zeviani M, Martí R. Mol Ther. 2014 May;22(5):901-7. doi: 10.1038/mt.2014.6. Epub 2014 Jan 22..

Mitochondrial myopathy with dystrophic features due to a novel mutation in the MTTM gene. Peverelli L, Gold CA, Naini AB, Tanji K, Akman HO, Hirano M, Dimauro S. Muscle Nerve. 2014 Aug;50(2):292-5. doi: 10.1002/mus.24262.

Mutant COQ2 in multiple-system atrophy. Quinzii CM, Hirano M, DiMauro S. N Engl J Med. 2014 Jul 3;371(1):81-2. doi: 10.1056/NEJMc1311763.

Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. Deeb KK, Bedoyan JK, Wang R, Sremba L, Schroeder MC, Grahame GJ, Boyer M, McCandless SE, Kerr DS, Zhang S. Mol Genet Metab. Rep. 2014 Aug 28;1:362-367.

The genetics of Leigh syndrome and its implications for clinical practice and risk management. Ruhoy IS, Saneto RP. Appl Clin Genet. 2014 Nov 13;7:221-34. doi: 10.2147/TACG.S46176. eCollection 2014.

Weighing in on Leber hereditary optic neuropathy: effects of mitochondrial mass. Hirano M. Brain. 2014 Feb;137(Pt 2):308-9. doi: 10.1093/brain/awu005.

Alpers-Huttenlocher syndrome. Saneto RP, Cohen BH, Copeland WC, Naviaux RK. Pediatr Neurol. 2013 Mar;48(3):167-78. doi: 10.1016/j.pediatrneurol.2012.09.014.

Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene. Melià MJ, Kubota A, Ortolano S, Vílchez JJ, Gámez J, Tanji K, Bonilla E, Palenzuela L, Fernández-Cadenas I, Pristoupilová A, García-Arumí E, Andreu AL, Navarro C, Hirano M, Martí R. Brain. 2013 May;136(Pt 5):1508-17. doi: 10.1093/brain/awt074. Epub 2013 Mar 29.

Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation. Paradas C, Camaño P, Otaegui D, Oz O, Emmanuele V, DiMauro S, Hirano M. JAMA Neurol. 2013 Nov;70(11):1425-8. doi: 10.1001/jamaneurol.2013.3185.

Mitochondrial cardioencephalomyopathy due to a novel SCO2 mutation in a Brazilian patient: case report and literature review. Gurgel-Giannetti J, Oliveira G, Brasileiro Filho G, Martins P, Vainzof M, Hirano M. JAMA Neurol. 2013 Feb;70(2):258-61. doi: 10.1001/jamaneurol.2013.595.

Mitochondrial disease in childhood: mtDNA encoded. Saneto RP, Sedensky MM. Neurotherapeutics. 2013 Apr;10(2):199-211. doi: 10.1007/s13311-012-0167-0.

Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture. DiMauro S. Neurology. 2013 Jul 16;81(3):281-91. doi: 10.1212/WNL.0b013e31829bfe89.

New treatments for mitochondrial disease-no time to drop our standards. Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. Nat Rev Neurol. 2013 Aug;9(8):474-81. doi: 10.1038/nrneurol.2013.129. Epub 2013 Jul 2.

176th ENMC International Workshop: diagnosis and treatment of coenzyme Q(1)(0) deficiency. Rahman S, Clarke CF, Hirano M. Neuromuscul Disord. Jan 2012;22(1):76-86. PMID: 21723727, PMCID: PMC3222743.

A novel POLG gene mutation in a patient with SANDO. Kurt B, Naini AB, Copeland WC, Lu J, Dimauro S, Hirano M. J Exp Integr Med. 2012;2(2):10.5455/jeim.200312.cr.001. doi: 10.5455/jeim.200312.cr.001.

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy. Ash DB, Papadimitriou D, Hays AP, Dimauro S, Hirano M. Arch Neurol. 2012 Sep;69(9):1190-2. doi: 10.1001/archneurol.2011.2600.

Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Marti R, Lopez LC, Hirano M. Methods Mol Biol. 2012;837:121-133. PMID: 22215544, PMCID: PMC4942128.

Infantile encephaloneuromyopathy and defective mitochondrial translation are due to a homozygous RMND1 mutation. Garcia-Diaz B, Barros MH, Sanna-Cherchi S, Emmanuele V, Akman HO, Ferreiro-Barros CC, Horvath R, Tadesse S, El Gharaby N, DiMauro S, De Vivo DC, Shokr A, Hirano M, Quinzii CM. Am J Hum Genet. 2012 Oct 5;91(4):729-36. doi: 10.1016/j.ajhg.2012.08.019. Epub 2012 Sep 27.

MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions. Garone C, Rubio JC, Calvo SE, Naini A, Tanji K, Dimauro S, Mootha VK, Hirano M. Arch Neurol. 2012 Dec;69(12):1648-51. doi: 10.1001/archneurol.2012.405.

Measurement of mitochondrial dNTP pools. Martí R, Dorado B, Hirano M. Methods Mol Biol. 2012;837:135-48. doi: 10.1007/978-1-61779-504-6_9.

POLG1 Arg953Cys mutation: expanded phenotype and recessive inheritance in a Brazilian family. Gurgel-Giannetti J, Camargos ST, Cardoso F, Hirano M, DiMauro S. Muscle Nerve. 2012 Mar;45(3):453-4. doi: 10.1002/mus.22330.

What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr?. Neeve VC, Samuels DC, Bindoff LA, van den Bosch B, Van Goethem G, Smeets H, Lombès A, Jardel C, Hirano M, Dimauro S, De Vries M, Smeitink J, Smits BW, de Coo IF, Saft C, Klopstock T, Keiling BC, Czermin B, Abicht A, Lochmüller H, Hudson G, Gorman GG, Turnbull DM, Taylor RW, Holinski-Feder E, Chinnery PF, Horvath R. Brain. 2012 Dec;135(Pt 12):3614-26. doi: 10.1093/brain/aws298.

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Halter J, Schüpbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krähenbühl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.

Hematopoietic gene therapy restores thymidine phosphorylase activity in a cell culture and a murine model of MNGIE. Torres-Torronteras J, Gómez A, Eixarch H, Palenzuela L, Pizzorno G, Hirano M, Andreu AL, Barquinero J, Martí R. Gene Ther. 2011 Aug;18(8):795-806. doi: 10.1038/gt.2011.24. Epub 2011 Mar 31.

Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Neurology. 2011 Nov 29;77(22):1965-71. doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.

Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation. Dorado B, Area E, Akman HO, Hirano M. Hum Mol Genet. Jan 1 2011;20(1):155-164. PMID: 20940150, PMCID: PMC3000681.

Primary and secondary CoQ(10) deficiencies in humans. Quinzii CM, Hirano M. Biofactors. Sep 2011;37(5):361-365. PMID: 21990098, PMCID: PMC3258494.

Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity. Villarroya J, Lara MC, Dorado B, Garrido M, García-Arumí E, Meseguer A, Hirano M, Vilà MR. Biochem Biophys Res Commun. 2011 Apr 8;407(2):333-8. doi: 10.1016/j.bbrc.2011.03.018. Epub 2011 Mar 5.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice. Villarroya J, Dorado B, Vilà MR, Garcia-Arumí E, Domingo P, Giralt M, Hirano M, Villarroya F. PLoS One. 2011;6(12):e29691. doi: 10.1371/journal.pone.0029691. Epub 2011 Dec 27.

A novel tRNA(Val) mitochondrial DNA mutation causing MELAS. Tanji K, Kaufmann P, Naini AB, Lu J, Parsons TC, Wang D, Willey JZ, Shanske S, Hirano M, Bonilla E, Khandji A, Dimauro S, Rowland LP. J Neurol Sci. 2008 Jul 15;270(1-2):23-7. doi: 10.1016/j.jns.2008.01.016. Epub 2008 Mar 7.

State-of-the-art 2023 on gene therapy for phenylketonuria. Martinez M, Harding CO, Schwank G, Thöny B. J Inherit Metab Dis. 2024 Jan;47(1):80-92. doi: 10.1002/jimd.12651. Epub 2023 Aug 3. PMID: 37401651; PMCID: PMC10764640

Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of the amino acid phenylalanine, which can build up to harmful levels if left untreated. Patients with PKU are treated with dietary therapy. However, these dietary restrictions are complicated and often difficult to follow, highlighting the need for new therapies and ultimately a cure.

In this review paper, researchers summarize, compare, and evaluate state-of-the-art gene therapy approaches for PKU. Methods include recombinant viral and non-viral vector delivery; gene addition; genome, gene, or base editing; and gene insertion or replacement. A list of current and planned clinical trials for PKU gene therapy is also included.

Authors note that this review can help advance scientific understanding and efficacy testing, paving the way for safe and efficient therapies for patients with PKU.

Phenylketonuria. van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Nat Rev Dis Primers. 2021 May 20;7(1):36. doi: 10.1038/s41572-021-00267-0.

Phenylketonuria (PKU; also known as phenylalanine hydroxylase (PAH) deficiency) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe intellectual disability, epilepsy and behavioural problems. Even though PAH deficiency is the most common defect of amino acid metabolism in humans, brain dysfunction in individuals with PKU is still not well understood and further research is needed to facilitate development of pathophysiology-driven treatments.

Retrospective analysis of 19 patients with 6-Pyruvoyl Tetrahydropterin Synthase Deficiency: Prolactin levels inversely correlate with growth. Manzoni F, Salvatici E, Burlina A, Andrews A, Pasquali M, Longo N. Mol Genet Metab. 2020 Dec;131(4):380-389. doi: 10.1016/j.ymgme.2020.11.004. Epub 2020 Nov 18. PMID: 33234470; PMCID: PMC7749858.

Pyruvoyl Tetrahydropterin Synthase (PTPS) Deficiency is the most common form of BH4 (tetrahydrobiopterin) deficiency resulting in hyperphenylalaninemia. It can have variable clinical severity and there is limited information on the clinical presentation, natural history and effectiveness of newborn screening for this condition.

Prospects for Cell-Directed Curative Therapy of Phenylketonuria (PKU). Harding CO. Mol Front J. 2019 Dec;3(2):110-121. doi: 10.1142/s2529732519400145. Epub 2019 Dec 12. PMID: 32524084; PMCID: PMC7286632.

This review discusses the potential for and the limitations of permanently curative cell-directed treatment of PKU (phenylketonuria, also known as phenylalanine hydroxylase (PAH) deficiency), including liver-directed gene therapy and gene editing, if initiated during early infancy.

AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review. Wang B, Bonkovsky HL, Lim JK, Balwani M. Gastroenterology. 2023 Mar;164(3):484-491. doi: 10.1053/j.gastro.2022.11.034. Epub 2023 Jan 13. PMID: 36642627.

Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study. Applequist J, Burroughs C, Merkel PA, Rothenberg M, Trapnell B, Desnick R, Sahin M, Krischer J. J Med Internet Res. 2023 Mar 14;25:e39262. doi: 10.2196/39262.

Evidence based consensus guidelines for diagnosis and management of Protoporphyria-Related liver dysfunction in erythropoietic protoporphyria and X-Linked protoporphyria. Levy C, Dickey AK, Wang B, Thapar M, Naik H, Keel SB, Saberi B, Beaven SW, Rudnick SR, Elmariah SB, Erwin AL, Goddu RJ, Hedstrom K, Leaf RK, Kazamel M, Mazepa M, Philpotts LL, Quigley J, Raef H, Ungar J, Anderson KE, Balwani M; Porphyrias Consortium of the Rare Diseases Clinical Network. Hepatology. 2023 Jul 27. doi: 10.1097/HEP.0000000000000546. Epub ahead of print. PMID: 37505211

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited, metabolic disorders characterized by the buildup of protoporphyrins (substances that bind metals to form complexes, such as the iron found in red blood cells). In addition to phototoxicity (severe pain during light exposure), patients with EPP and XLP often experience liver dysfunction. However, there is a lack of published information on the management of liver disease in these patients.

In this study, researchers established evidence-based guidelines for the diagnosis and management of liver disease in protoporphyrias. A group of 15 clinicians from the Porphyrias Consortium—with expertise in porphyrias and hepatology, hematology, and genetics—conducted a systematic literature review to develop new recommendations.

The resulting guidelines address important clinical topics in protoporphyrias and liver disease, including interventions and therapies based on severity. Authors note that these guidelines may not only improve patient care, but also inspire new collaborative research.

How I treat erythropoietic protoporphyria and X-linked protoporphyria. Leaf RK, Dickey AK. Blood. 2023 Jun 15;141(24):2921-2931. doi: 10.1182/blood.2022018688.

Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C. Bonkovsky HL, Rudnick SP, Ma CD, Overbey JR, Wang K, Faust D, Hallberg C, Hedstrom K, Naik H, Moghe A, Anderson KE. Dig Dis Sci. 2023 Feb 22:1–9. doi: 10.1007/s10620-023-07859-8. Epub ahead of print. PMID: 36811718; PMCID: PMC9945827.

A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria. Balwani M, Naik H, Overbey JR, Bonkovsky HL, Bissell DM, Wang B, Phillips JD, Desnick RJ, Anderson KE. Mol Genet Metab Rep. 2022 Nov 14;33:100939. doi: 10.1016/j.ymgmr.2022.100939. PMID: 36406817; PMCID: PMC9672425.

ABCB6 polymorphisms are not overly represented in patients with porphyria. Farrell CP, Nicolas G, Desnick RJ, Parker CJ, Lamoril J, Gouya L, Karim Z, Tchernitchko D, Chan B, Puy H, Phillips JD. Blood Adv. 2022 Feb 8;6(3):760-766. doi: 10.1182/bloodadvances.2021005484. PMID: 34724702; PMCID: PMC8945301.

The porphyrias are a group of rare, inherited, metabolic disorders characterized by elevated porphyrin or porphyrin precursor levels that are caused by deficiencies in one of eight enzymes necessary for heme production. Recent studies have suggested that the genotype of the transporter protein ABCB6 contributes to the porphyria phenotype. To address this proposed link, researchers analyzed data from a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria. Results showed that the ABCB6 genotype did not correlate with disease severity. Authors conclude that genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.

Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence-based screening assay. Ma CD, Van Horn CG, Wan M, Bishop C, Bonkovsky HL. Pharmacol Res Perspect. 2022 Jun;10(3):e00951. doi: 10.1002/prp2.951. PMID: 35445802; PMCID: PMC9022196.

Acute hepatic porphyrias (AHPs)—including ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria—are a subtype of porphyrias classified as having a hepatic (liver) origin. In patients with AHPs, some drugs and chemicals may trigger or exacerbate acute porphyric attacks. However, there is currently no standard model to assess and predict the likelihood of drugs and chemicals to induce these attacks. In this study, researchers aimed to develop a fluorescence-based in vitro assay for this purpose. The team studied four different hepatic cell culture models. They found that LMH cell cultures in multi-well plates are an inexpensive, robust, and simple system to predict the porphyrogenicity of compounds that may exacerbate the AHPs.

Elagolix is porphyrogenic and may induce porphyric attacks in patients with the acute hepatic porphyrias. Ma CD, Bonkovsky HL. Mol Genet Metab Rep. 2022 Sep 7;33:100915. doi: 10.1016/j.ymgmr.2022.100915. PMID: 36105850; PMCID: PMC9465260.

Eslicarbazepine acetate is porphyrogenic and should be used with caution in patients with the acute hepatic porphyrias. Ma CD, Bonkovsky HL. Front Pharmacol. 2022 Sep 6;13:953961. doi: 10.3389/fphar.2022.953961. PMID: 36147354; PMCID: PMC9485715.

Evidence-based consensus guidelines for the diagnosis and management of erythropoietic protoporphyria and X-linked protoporphyria. Dickey AK, Naik H, Keel SB, Levy C, Beaven SW, Elmariah SB, Erwin AL, Goddu RJ, Hedstrom K, Leaf RK, Kazamel M, Mazepa M, Philpotts LL, Quigley J, Raef H, Rudnick SR, Saberi B, Thapar M, Ungar J, Wang B, Balwani M; Porphyrias Consortium of the Rare Diseases Clinical Research Network. J Am Acad Dermatol. 2022 Aug 27:S0190-9622(22)02611-1. doi: 10.1016/j.jaad.2022.08.036. Epub ahead of print. PMID: 36041558.

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare, inherited, metabolic disorders characterized by build-up of porphyrins. Porphyrins are substances that bind metals to form complexes, such as the iron found in red blood cells. The hallmark symptoms include phototoxicity (severe pain during light exposure) and photosensitivity (skin hyperreactivity to light). Due to the rarity of EPP and XLP, physicians often have limited expertise with these disorders, which can lead to delays in diagnosis. In this study, researchers developed evidence-based consensus guidelines for the diagnosis, monitoring, and management of EPP and XLP. First, the team conducted a systematic literature review. Next, they divided topics among subcommittees of experts to reach a consensus on guidelines. The new guidelines discuss biochemical and genetic testing for diagnosis, prevention of symptoms, management of acute phototoxicity, and pharmacologic (drug or medication) and non-pharmacologic treatment options. Researchers also discuss management, including the importance of ongoing monitoring, guidance on pregnancy and surgery, and the safety of other therapies. Authors note that these guidelines can aid in early diagnosis and management of these disorders.

Pain in acute hepatic porphyrias: Updates on pathophysiology and management. Kazamel M, Pischik E, Desnick RJ. Front Neurol. 2022 Nov 21;13:1004125. doi: 10.3389/fneur.2022.1004125. PMID: 36479055; PMCID: PMC9719963.

Evidence in the UK Biobank for the underdiagnosis of erythropoietic protoporphyria. Dickey AK, Quick C, Ducamp S, Zhu Z, Feng YA, Naik H, Balwani M, Anderson KE, Lin X, Phillips JE, Rebeiz L, Bonkovsky HL, McGuire BM, Wang B, Chasman DI, Smoller JW, Fleming MD, Christiani DC. Genet Med. 2021 Jan;23(1):140-148. doi: 10.1038/s41436-020-00951-8. Epub 2020 Sep 2.

In this study of genetic data from 50,000 participants in the UK Biobank, researchers found that the number of individuals with the genetic pairing that causes EPP was seven times higher than the number of individuals who had been diagnosed. The prevalance of EPP in the data set turned out to be 1 in 17,000 people. See blog post.

Novel treatment options for acute hepatic porphyrias. Wang B. Curr Opin Gastroenterol. 2021 May 1;37(3):194-199. doi: 10.1097/MOG.0000000000000734.

Porphyrias in the Age of Targeted Therapies. Erwin AL, Balwani M. Diagnostics (Basel). 2021 Sep 29;11(10):1795. doi: 10.3390/diagnostics11101795.

The acute hepatic porphyrias. Wang B. Transl Gastroenterol Hepatol. 2021 Apr 5;6:24. doi: 10.21037/tgh-2020-01. eCollection 2021.

The ubiquitous mitochondrial protein unfoldase CLPX regulates erythroid heme synthesis by control of iron utilization and heme synthesis enzyme activation and turnover. Rondelli CM, Perfetto M, Danoff A, Bergonia H, Gillis S, O'Neill L, Jackson L, Nicolas G, Puy H, West R, Phillips JD, Yien YY. J Biol Chem. 2021 Aug;297(2):100972. doi: 10.1016/j.jbc.2021.100972. Epub 2021 Jul 16.

Porphyrias are rare disorders caused by an abnormality in the heme production process. Heme enables our blood cells to carry oxygen and helps break down chemical compounds in the liver. Erythropoietic protoporphyria patients experience a build-up of protoporphyrin in the bone marrow, red blood cells, blood plasma, skin, and eventually liver. This buildup can cause extreme sensitivity to sunlight, liver damage, and other problems. The protein CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X) promotes heme synthesis. Researchers seeking to better understand the ways CLPX regulates heme synthesis in red blood cells undertook genomic studies in yeast, zebrafish, and mouse models. They found that CLPX mutations may cause anemia and porphyria via dysregulation of ALAS, FECH, and PPOX activities, as well as of iron metabolism. They conclude that unraveling the complexities of CLPX function will be key for designing therapies for these rare diseases.

5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin. Lahiji AP, Anderson KE, Chan A, Simon A, Desnick RJ, Ramanujam VMS. Mol Genet Metab. 2020 Dec;131(4):418-423. doi: 10.1016/j.ymgme.2020.10.011. Epub 2020 Oct 26.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks. Gouya L, Ventura P, Balwani M, Bissell DM, Rees DC, Stölzel U, Phillips JD, Kauppinen R, Langendonk JG, Desnick RJ, Deybach JC, Bonkovsky HL, Parker C, Naik H, Badminton M, Stein PE, Minder E, Windyga J, Bruha R, Cappellini MD, Sardh E, Harper P, Sandberg S, Aarsand AK, Andersen J, Alegre F, Ivanova A, Talbi N, Chan A, Querbes W, Ko J, Penz C, Liu S, Lin T, Simon A, Anderson KE. Hepatology. 2020 May;71(5):1546-1558. doi: 10.1002/hep.30936. Epub 2019 Nov 7.

Editorial: hepatitis C and porphyria cutanea tarda in 2020. Rudnick S, Bonkovsky HL. Aliment Pharmacol Ther. 2020 Jun;51(12):1432-1434. doi: 10.1111/apt.15728.

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria. Naik H, Overbey JR, Montgomery GH, Winkel G, Balwani M, Anderson KE, Bissell DM, Bonkovsky HL, Phillips JD, Wang B, McGuire B, Keel S, Levy C, Erwin A, Desnick RJ. Genet Med. 2020 Mar;22(3):590-597. doi: 10.1038/s41436-019-0683-y. Epub 2019 Nov 6.

Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium. Saberi B, Naik H, Overbey JR, Erwin AL, Anderson KE, Bissell DM, Bonkovsky HL, Phillips JD, Wang B, K Singal A, M McGuire B, Desnick RJ, Balwani M. Hepatology. 2021 May;73(5):1736-1746. doi: 10.1002/hep.31460. Epub 2020 Dec 11. PMID: 32681675.

The acute hepatic porphyrias (AHP) are a family of rare genetic diseases that present with acute attacks, nausea, and vomiting which can last for several days. These disorders can also have chronic symptoms and an increased risk for long-term manifestations. The risk for hepatocellular carcinoma (HCC) is increased in patients with acute hepatic porphyrias. In order to characterize the symptoms, outcomes, and frequency of HCC in patients with AHP in the United States, researchers undertook a multicenter, longitudinal study. Among 327 patients with AHP, 5 (1.5%) were diagnosed with HCC. Cirrhosis was not present in AHP patients with HCC, unlike what is typically seen with other chronic liver diseases. Study authors recommend that patients with AHP should be screened for HCC beginning at age 50.

Acute hepatic porphyrias: Current diagnosis & management. Anderson KE. Mol Genet Metab. 2019 Nov;128(3):219-227. doi: 10.1016/j.ymgme.2019.07.002. Epub 2019 Jul 5.

Characterization of the hepatic transcriptome following phenobarbital induction in mice with AIP. Chen B, Wang M, Gan L, Zhang B, Desnick RJ, Yasuda M. Mol Genet Metab. 2019 Nov;128(3):382-390. doi: 10.1016/j.ymgme.2018.12.010. Epub 2019 Jan 6.

Congenital erythropoietic porphyria: Recent advances. Erwin AL, Desnick RJ. Mol Genet Metab. 2019 Nov;128(3):288-297. doi: 10.1016/j.ymgme.2018.12.008. Epub 2018 Dec 27.

Erythropoietic Protoporphyria and X-Linked Protoporphyria: pathophysiology, genetics, clinical manifestations, and management. Balwani M. Mol Genet Metab. 2019 Nov;128(3):298-303. doi: 10.1016/j.ymgme.2019.01.020. Epub 2019 Jan 24.

Harderoporphyria: Case of lifelong photosensitivity associated with compound heterozygous coproporphyrinogen oxidase (CPOX) mutations. Moghe A, Ramanujam VMS, Phillips JD, Desnick RJ, Anderson KE. Mol Genet Metab Rep. 2019 Feb 19;19:100457. doi: 10.1016/j.ymgmr.2019.100457. eCollection 2019 Jun.

Heme biosynthesis and the porphyrias. Phillips JD. Mol Genet Metab. 2019 Nov;128(3):164-177. doi: 10.1016/j.ymgme.2019.04.008. Epub 2019 Apr 22.

Homozygous hydroxymethylbilane synthase knock-in mice provide pathogenic insights into the severe neurological impairments present in human homozygous dominant acute intermittent porphyria. Yasuda M, Gan L, Chen B, Yu C, Zhang J, Gama-Sosa MA, Pollak DD, Berger S, Phillips JD, Edelmann W, Desnick RJ. Hum Mol Genet. 2019 Jun 1;28(11):1755-1767. doi: 10.1093/hmg/ddz003.

Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause acute intermittent porphyria. Chen B, Solis-Villa C, Erwin AL, Balwani M, Nazarenko I, Phillips JD, Desnick RJ, Yasuda M. J Inherit Metab Dis. 2019 Jan;42(1):186-194. doi: 10.1002/jimd.12040.

International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias. Chen B, Whatley S, Badminton M, Aarsand AK, Anderson KE, Bissell DM, Bonkovsky HL, Cappellini MD, Floderus Y, Friesema ECH, Gouya L, Harper P, Kauppinen R, Loskove Y, Martásek P, Phillips JD, Puy H, Sandberg S, Schmitt C, To-Figueras J, Weiss Y, Yasuda M, Deybach JC, Desnick RJ. Genet Med. 2019 Nov;21(11):2605-2613. doi: 10.1038/s41436-019-0537-7. Epub 2019 May 10.

Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies. Yasuda M, Desnick RJ. Mol Genet Metab. 2019 Nov;128(3):332-341. doi: 10.1016/j.ymgme.2019.01.007. Epub 2019 Jan 18.

Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs). Bonkovsky HL, Dixon N, Rudnick S. Mol Genet Metab. 2019 Nov;128(3):213-218. doi: 10.1016/j.ymgme.2019.03.002. Epub 2019 Mar 6.

Pilot study of mitochondrial bioenergetics in subjects with acute porphyrias. Dixon N, Li T, Marion B, Faust D, Dozier S, Molina A, Rudnick S, Bonkovsky HL. Mol Genet Metab. 2019 Nov;128(3):228-235. doi: 10.1016/j.ymgme.2019.05.010. Epub 2019 May 20.

Porphyria cutanea tarda and hepatoerythropoietic porphyria: Identification of 19 novel uroporphyrinogen III decarboxylase mutations. Weiss Y, Chen B, Yasuda M, Nazarenko I, Anderson KE, Desnick RJ. Mol Genet Metab. 2019 Nov;128(3):363-366. doi: 10.1016/j.ymgme.2018.11.013. Epub 2018 Nov 28.

Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury. Maitra D, Bragazzi Cunha J, Elenbaas JS, Bonkovsky HL, Shavit JA, Omary MB. Cell Mol Gastroenterol Hepatol. 2019;8(4):535-548. doi: 10.1016/j.jcmgh.2019.06.006. Epub 2019 Jun 21.

Psychosocial issues in erythropoietic protoporphyria - the perspective of parents, children, and young adults: A qualitative study. Naik H, Shenbagam S, Go AM, Balwani M. Mol Genet Metab. 2019 Nov;128(3):314-319. doi: 10.1016/j.ymgme.2019.01.023. Epub 2019 Jan 26.

Recent advances on porphyria genetics: Inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes. Yasuda M, Chen B, Desnick RJ. Mol Genet Metab. 2019 Nov;128(3):320-331. doi: 10.1016/j.ymgme.2018.11.012. Epub 2018 Nov 30.

Results of a pilot study of isoniazid in patients with erythropoietic protoporphyria. Parker CJ, Desnick RJ, Bissel MD, Bloomer JR, Singal A, Gouya L, Puy H, Anderson KE, Balwani M, Phillips JD. Mol Genet Metab. 2019 Nov;128(3):309-313. doi: 10.1016/j.ymgme.2019.07.017. Epub 2019 Jul 31.

Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria. Pulgar VM, Yasuda M, Gan L, Desnick RJ, Bonkovsky HL. Mol Genet Metab. 2019 Nov;128(3):376-381. doi: 10.1016/j.ymgme.2019.01.005. Epub 2019 Jan 7.

Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria. Phillips J, Farrell C, Wang Y, Singal AK, Anderson K, Balwani M, Bissell M, Bonkovsky H, Seay T, Paw B, Desnick R, Bloomer J. Mol Genet Metab. 2019 Nov;128(3):391-395. doi: 10.1016/j.ymgme.2018.10.005. Epub 2018 Oct 22.

Acute Hepatic Porphyrias: Review and Recent Progress. Wang B, Rudnick S, Cengia B, Bonkovsky HL. Hepatol Commun. 2018 Dec 20;3(2):193-206. doi: 10.1002/hep4.1297. eCollection 2019 Feb.

Diagnostic Delay in Erythropoietic Protoporphyria. Lala SM, Naik H, Balwani M. J Pediatr. 2018 Nov;202:320-323.e2. doi: 10.1016/j.jpeds.2018.06.001. Epub 2018 Jul 2.

FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. Yien YY, Shi J, Chen C, Cheung JTM, Grillo AS, Shrestha R, Li L, Zhang X, Kafina MD, Kingsley PD, King MJ, Ablain J, Li H, Zon LI, Palis J, Burke MD, Bauer DE, Orkin SH, Koehler CM, Phillips JD, Kaplan J, Ward DM, Lodish HF, Paw BH. J Biol Chem. 2018 Dec 21;293(51):19797-19811. doi: 10.1074/jbc.RA118.002742. Epub 2018 Oct 26.

Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis. Salameh H, Sarairah H, Rizwan M, Kuo YF, Anderson KE, Singal AK. Br J Dermatol. 2018 Dec;179(6):1351-1357. doi: 10.1111/bjd.16741. Epub 2018 Jul 26.

Acute hepatic porphyrias: Recommendations for evaluation and long-term management. Balwani M, Wang B, Anderson KE, Bloomer JR, Bissell DM, Bonkovsky HL, Phillips JD, Desnick RJ; Porphyrias Consortium of the Rare Diseases Clinical Research Network. Hepatology. 2017 Oct;66(4):1314-1322. doi: 10.1002/hep.29313. Epub 2017 Sep 4.

Clinical, Biochemical, and Genetic Characterization of North American Patients With Erythropoietic Protoporphyria and X-linked Protoporphyria. Balwani M, Naik H, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, Phillips JD, Overbey JR, Wang B, Singal AK, Liu LU, Desnick RJ. JAMA Dermatol. 2017 Aug 1;153(8):789-796. doi: 10.1001/jamadermatol.2017.1557.

Hepatitis C Treatment in Patients With Porphyria Cutanea Tarda. Singal AK, Venkata KVR, Jampana S, Islam FU, Anderson KE. Am J Med Sci. 2017 Jun;353(6):523-528. doi: 10.1016/j.amjms.2017.03.007. Epub 2017 Mar 8.

Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Yien YY, Ducamp S, van der Vorm LN, Kardon JR, Manceau H, Kannengiesser C, Bergonia HA, Kafina MD, Karim Z, Gouya L, Baker TA, Puy H, Phillips JD, Nicolas G, Paw BH. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8045-E8052. doi: 10.1073/pnas.1700632114. Epub 2017 Sep 5.

A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase. Piel RB 3rd, Shiferaw MT, Vashisht AA, Marcero JR, Praissman JL, Phillips JD, Wohlschlegel JA, Medlock AE. Biochemistry. 2016 Sep 20;55(37):5204-17. doi: 10.1021/acs.biochem.6b00756. Epub 2016 Sep 9.

Acute Intermittent Porphyria in children: A case report and review of the literature. Balwani M, Singh P, Seth A, Debnath EM, Naik H, Doheny D, Chen B, Yasuda M, Desnick RJ. Mol Genet Metab. 2016 Dec;119(4):295-299. doi: 10.1016/j.ymgme.2016.10.005. Epub 2016 Oct 15.

Acute Intermittent Porphyria: Predicted Pathogenicity of HMBS Variants Indicates Extremely Low Penetrance of the Autosomal Dominant Disease. Chen B, Solis-Villa C, Hakenberg J, Qiao W, Srinivasan RR, Yasuda M, Balwani M, Doheny D, Peter I, Chen R, Desnick RJ. Hum Mutat. 2016 Nov;37(11):1215-1222. doi: 10.1002/humu.23067. Epub 2016 Sep 5.

Advances in the management of erythropoietic protoporphyria - role of afamelanotide. Lane AM, McKay JT, Bonkovsky HL. Appl Clin Genet. 2016 Dec 12;9:179-189. doi: 10.2147/TACG.S122030. eCollection 2016.

Experiences and concerns of patients with recurrent attacks of acute hepatic porphyria: A qualitative study. Naik H, Stoecker M, Sanderson SC, Balwani M, Desnick RJ. Mol Genet Metab. 2016 Nov;119(3):278-283. doi: 10.1016/j.ymgme.2016.08.006. Epub 2016 Aug 24.

Hepatotoxicity Associated with the Use of Anti-TNF-α Agents. French JB, Bonacini M, Ghabril M, Foureau D, Bonkovsky HL. Drug Saf. 2016 Mar;39(3):199-208. doi: 10.1007/s40264-015-0366-9.

Protoporphyrin IX: the Good, the Bad, and the Ugly. Sachar M, Anderson KE, Ma X. J Pharmacol Exp Ther. 2016 Feb;356(2):267-75. doi: 10.1124/jpet.115.228130. Epub 2015 Nov 20.

The D519G Polymorphism of Glyceronephosphate O-Acyltransferase Is a Risk Factor for Familial Porphyria Cutanea Tarda. Farrell CP, Overbey JR, Naik H, Nance D, McLaren GD, McLaren CE, Zhou L, Desnick RJ, Parker CJ, Phillips JD. PLoS One. 2016 Sep 23;11(9):e0163322. doi: 10.1371/journal.pone.0163322. eCollection 2016.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria. Brancaleoni V, Balwani M, Granata F, Graziadei G, Missineo P, Fiorentino V, Fustinoni S, Cappellini MD, Naik H, Desnick RJ, Di Pierro E. Clin Genet. 2016 Jan;89(1):20-6. doi: 10.1111/cge.12562. Epub 2015 Feb 17.

A method for determining δ-aminolevulinic acid synthase activity in homogenized cells and tissues. Bergonia HA, Franklin MR, Kushner JP, Phillips JD. Clin Biochem. 2015 Aug;48(12):788-95. doi: 10.1016/j.clinbiochem.2015.04.023. Epub 2015 May 8.

Acute Hepatic Porphyria. Bissell DM, Wang B. J Clin Transl Hepatol. 2015 Mar;3(1):17-26. doi: 10.14218/JCTH.2014.00039. Epub 2015 Mar 15.

Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG, Balwani M, Anderson KE, et al. N Engl J Med. Jul 2 2015;373(1):48-59. PMID: 26132941.

Bone marrow transplant for X-linked protoporphyria with severe hepatic fibrosis. Butler DF, Ginn KF, Daniel JF, Bloomer JR, Kats A, Shreve N, Myers GD. Pediatr Transplant. 2015 Jun;19(4):E106-10. doi: 10.1111/petr.12472. Epub 2015 Apr 9.

Comparison of functional variants in IFNL4 and IFNL3 for association with HCV clearance. O'Brien TR, Pfeiffer RM, Paquin A, Lang Kuhs KA, Chen S, Bonkovsky HL, Edlin BR, Howell CD, Kirk GD, Kuniholm MH, Morgan TR, Strickler HD, Thomas DL, Prokunina-Olsson L. J Hepatol. 2015 Nov;63(5):1103-10. doi: 10.1016/j.jhep.2015.06.035. Epub 2015 Jul 15.

Exome sequencing for molecular characterization of non-HFE hereditary hemochromatosis. Farrell CP, Parker CJ, Phillips JD. Blood Cells Mol Dis. 2015 Aug;55(2):101-3. doi: 10.1016/j.bcmd.2015.04.002. Epub 2015 May 1.

Homeostasis of iron and hepcidin in erythropoietic protoporphyria. Bossi K, Lee J, Schmeltzer P, Holburton E, Groseclose G, Besur S, Hwang S, Bonkovsky HL. Eur J Clin Invest. 2015 Oct;45(10):1032-41. doi: 10.1111/eci.12503. Epub 2015 Sep 2.

Identification of the Mitochondrial Heme Metabolism Complex. Medlock AE, Shiferaw MT, Marcero JR, Vashisht AA, Wohlschlegel JA, Phillips JD, Dailey HA. PLoS One. 2015 Aug 19;10(8):e0135896. doi: 10.1371/journal.pone.0135896. eCollection 2015.

Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria. Egan DN, Yang Z, Phillips J, Abkowitz JL. Blood. 2015 Jul 9;126(2):257-61. doi: 10.1182/blood-2014-07-584664. Epub 2015 May 13.

Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver. Yasuda M, Erwin AL, Liu LU, Balwani M, Chen B, Kadirvel S, Gan L, Fiel MI, Gordon RE, Yu C, Clavero S, Arvelakis A, Naik H, Martin LD, Phillips JD, Anderson KE, Sadagoparamanujam VM, Florman SS, Desnick RJ. Mol Med. 2015 Jun 5;21(1):487-95. doi: 10.2119/molmed.2015.00099.

Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. Dailey HA, Gerdes S, Dailey TA, Burch JS, Phillips JD. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2210-5. doi: 10.1073/pnas.1416285112. Epub 2015 Feb 2.

Pitfalls in Erythrocyte Protoporphyrin Measurement for Diagnosis and Monitoring of Protoporphyrias. Gou EW, Balwani M, Bissell DM, Bloomer JR, Bonkovsky HL, Desnick RJ, Naik H, Phillips JD, Singal AK, Wang B, Keel S, Anderson KE. Clin Chem. 2015 Dec;61(12):1453-6. doi: 10.1373/clinchem.2015.245456. Epub 2015 Oct 19.

Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias. Ramanujam VS, Anderson KE. Curr Protoc Hum Genet. 2015 Jul 1;86:17.20.1-17.20.26. doi: 10.1002/0471142905.hg1720s86.

Recent insights into the biological functions of liver fatty acid binding protein 1. Wang G, Bonkovsky HL, de Lemos A, Burczynski FJ. J Lipid Res. 2015 Dec;56(12):2238-47. doi: 10.1194/jlr.R056705. Epub 2015 Oct 6.

Role of delta-aminolevulinic acid in the symptoms of acute porphyria. Bissell DM, Lai JC, Meister RK, Blanc PD. Am J Med. 2015 Mar;128(3):313-7. doi: 10.1016/j.amjmed.2014.10.026. Epub 2014 Nov 8.

Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium. Bonkovsky HL, Maddukuri VC, Yazici C, Anderson KE, Bissell DM, Bloomer JR, Phillips JD, Naik H, Peter I, Baillargeon G, Bossi K, Gandolfo L, Light C, Bishop D, Desnick RJ. Am J Med. 2014 Dec;127(12):1233-41. doi: 10.1016/j.amjmed.2014.06.036. Epub 2014 Jul 10.

Clinically important features of porphyrin and heme metabolism and the porphyrias. Besur S, Hou W, Schmeltzer P, Bonkovsky HL. Metabolites. 2014 Nov 3;4(4):977-1006. doi: 10.3390/metabo4040977.

Liver transplantation in the management of porphyria. Singal AK, Parker C, Bowden C, Thapar M, Liu L, McGuire BM. Hepatology. 2014 Sep;60(3):1082-9. doi: 10.1002/hep.27086. Epub 2014 Jul 29.

RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice. Yasuda M, Gan L, Chen B, Kadirvel S, Yu C, Phillips JD, New MI, Liebow A, Fitzgerald K, Querbes W, Desnick RJ. Proc Natl Acad Sci U S A. 2014 May 27;111(21):7777-82. doi: 10.1073/pnas.1406228111. Epub 2014 May 12.

TMEM14C is required for erythroid mitochondrial heme metabolism. Yien YY, Robledo RF, Schultz IJ, Takahashi-Makise N, Gwynn B, Bauer DE, Dass A, Yi G, Li L, Hildick-Smith GJ, Cooney JD, Pierce EL, Mohler K, Dailey TA, Miyata N, Kingsley PD, Garone C, Hattangadi SM, Huang H, Chen W, Keenan EM, Shah DI, Schlaeger TM, DiMauro S, Orkin SH, Cantor AB, Palis J, Koehler CM, Lodish HF, Kaplan J, Ward DM, Dailey HA, Phillips JD, Peters LL, Paw BH. J Clin Invest. 2014 Oct;124(10):4294-304. doi: 10.1172/JCI76979. Epub 2014 Aug 26.

A Combined Clinical Index for the Diagnosis of Acute Porphyria. Wang B, Bissell D, Lai J, Cimino T, Porphyrias Consortium. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Acute Intermittent Porphyria: Identification of 19 Novel Hydroxymethylbilane Synthase Mutations and Functional Characterization of Four Novel Missense Mutations. Ludtke A, Yasuda M, Gan L, et al. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Acute Intermittent Porphyria: Identification of 23 Novel Hydroxymethylbilane Synthase Mutations and Functional Characterization of Six Novel Missense Mutations. Ludtke A, Yasuda M, Lin G, et al. ACMG Annual Clinical Genetics Meeting. Phoenix, AZ2013.

Acute intermittent porphyria [AIP] in the United States: features of the first 82 cases enrolled in the longitudinal study of the porphyria consortium [PC]. Maddukuri V, Yazici C, Anderson K, et al. Maddukuri V, Yazici C, Anderson K, et al. Acute intermittent porphyria [AIP] in the United States: features of the first 82 cases enrolled in the longitudinal study of the porphyria consortium [PC]. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Circadian rhythms in acute intermittent porphyria--a pilot study. Larion S, Caballes FR, Hwang SI, Lee JG, Rossman WE, Parsons J, Steuerwald N, Li T, Maddukuri V, Groseclose G, Finkielstein CV, Bonkovsky HL. Eur J Clin Invest. 2013 Jul;43(7):727-39. doi: 10.1111/eci.12102. Epub 2013 May 8.

Circadian rhythms in acute intermittent porphyria—a pilot study. Larion S, Caballes F, Hwang S, et al. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Congenital Erythropoietic Porphyria. Erwin A, Balwani M, Desnick RJ. In: Pagon RA, Adam MP, Bird TD, et al., eds. GeneReviews(R). Seattle WA: University of Washington, Seattle; 1993. PMID: 24027798.

Congenital erythropoietic porphyria. Mittal S, Anderson KE. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2013.

Diagnosis of feline acute intermittent porphyria presenting with erythrodontia requires molecular analyses. Clavero S, Ahuja Y, Bishop DF, Kwait B, Haskins ME, Giger U, Desnick RJ. Vet J. 2013 Dec;198(3):720-2. doi: 10.1016/j.tvjl.2013.10.008. Epub 2013 Oct 10.

Erythropoietic Protoporphyria and X-Linked Protoporphyria in the United States: Results from the Longitudinal Study of the NIH/RDCRN Porphyrias Consortium. Balwani M, Naik H, Peter I, et al. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Experience with a Pilot Skype Internet Support Group for Symptomatic Patients with Acute Intermittent Porphyria. Naik H, Balwani M, Doheny D, Liu L, Desnick R. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

First US Orthotopic Liver Transplant for Intractable Acute Intermittent Porphyria. Ludtke A, Yasuda M, Balwani M, et al. The American Society of Human Genetics 63rd Annual Meeting. Boston, MA2013.

Frequency of Porphyria Testing in a National Health Care Database. Gou E, Singh A, Pierson K, Wilkinson G, Anderson K. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Heme status affects human hepatic messenger RNA and microRNA expression. Bonkovsky HL, Hou W, Steuerwald N, et al. World J Gastroenterol. Mar 14 2013;19(10):1593-1601. PMID: 23538684, PMCID: PMC3602476.

Hepatoerythropoietic Porphyria. Liu LU, Phillips J, Bonkovsky H. In: Pagon RA, Adam MP, Bird TD, et al., eds. GeneReviews(R). Seattle WA: University of Washington, Seattle; 1993. PMID: 24175354.

Hereditary coproporphyria [HCP] and variegate porphyria [VP] in the United States: Initial results from the longitudinal study of the porphyria consortium [PC]. Yazici C, Maddukuri V, Anderson K, et al. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. Balwani M, Doheny D, Bishop DF, Nazarenko I, Yasuda M, Dailey HA, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, Phillips JD, Liu L, Desnick RJ; Porphyrias Consortium of the National Institutes of Health Rare Diseases Clinical Research Network. Mol Med. 2013 Apr 30;19(1):26-35. doi: 10.2119/molmed.2012.00340.

Low-dose hydroxychloroquine to treat or prevent relapse of porphyria cutanea tarda during hepatitis C treatment. Singal A, Jampana S, Kormos-Hallberg C, Anderson K. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Metabolic Analysis in Transgenic Mouse Models of Acute Intermittent Porphyria (AIP). Mittal S, Yasuda M, Desnick R, Anderson K. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Molecular expression and characterization of erythroid-specific 5-aminolevulinate synthase gain-of-function mutations causing X-linked protoporphyria. Bishop DF, Tchaikovskii V, Nazarenko I, Desnick RJ. Mol Med. 2013 Mar 5;19(1):18-25. doi: 10.2119/molmed.2013.00003.

Mutation analysis of 155 North American Patients with Erythropoietic Protoporphyria reveals novel Ferrochelatase Mutations and a high prevalence of X-Linked Protoporphyria due to previous and novel 5-Aminolevulinate Synthase 2 mutations. Balwani M, Bishop D, Nazarenko I, et al. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Porphyria Cutanea Tarda, Type II. Liu LU, Phillips J, Bonkovsky H. In: Pagon RA, Adam MP, Bird TD, et al., eds. GeneReviews(R). Seattle WA: University of Washington, Seattle; 1993. PMID: 23741761.

Porphyria studies in Cyp1A2-/- and wild type mice suggest that heme regulation of ALA-synthase transcription and mitochondrial membrane translocation can be separated based on heme supply-and-demand. Phillips J, Warby C, Bergonia H, Marcero J, Parker C, Franklin M. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Porphyrin and Heme Metabolism and the Porphyrias. Bonkovsky HL, Guo J-T, Hou W, Li T, Narang T, Thapar M. Comprehensive Physiology: John Wiley & Sons, Inc.; 2013:365-401.

Relapse of porphyria cutanea tarda after achieving remission with phlebotomy or low dose hydroxychloroquine. Singal A, Gou E, Albuerne M, Kormos-Hallberg C, Anderson K. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

Risk factors for porphyria cutanea tarda -the iron/HFE connection. Bonkovsky HL. Liver Int. Jan 2013;33(1):162. PMID: 23121614.

Synthase Gain-of-Function Mutations Causing X-Linked Protoporphyria. Bishop D, Tchaikovskii V, Nazarenko I, Desnick R. Paper presented at: Annual Assembly of the Swiss Society of Clinical Chemistry & International Congress of Porphyrins and Porphyrias; May 16-18, 2013; Lucerne, Switzerland.

The Porphyrias. Gou E, Anderson K. In: Hamblin M, Huang Y, eds. Handbook of Photomedicine. Boca Raton, FL: Taylor and Francis; 2013.

Variegate Porphyria. Anderson KE, Singal AK. GeneReviews. Seattle WA: University of Washington, Seattle; 1993.

X-Linked Protoporphyria. Balwani M, Bloomer J, Desnick R. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, eds. GeneReviews. Seattle WA: University of Washington, Seattle; 1993. PMID: 23409301.

ABCB6 mutations cause ocular coloboma. Wang L, He F, Bu J, Zhen Y, Liu X, Du W, Dong J, Cooney JD, Dubey SK, Shi Y, Gong B, Li J, McBride PF, Jia Y, Lu F, Soltis KA, Lin Y, Namburi P, Liang C, Sundaresan P, Paw BH, Li W, Li DY, Phillips JD, Yang Z. Am J Hum Genet. 2012 Jan 13;90(1):40-8. doi: 10.1016/j.ajhg.2011.11.026. Epub 2012 Jan 5.

Disorders of heme biosynthesis In: J-M S, Van den Berghe G, Walter JH, eds. Lourenco CM, Lee C, Anderson KE. In: J-M S, Van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 5th ed. Berlin: Springer- Verlag; 2012:519-532.

Erythropoietic Protoporphyria, Autosomal Recessive. Balwani M, Bloomer J, Desnick R. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, eds. GeneReviews. Seattle WA: University of Washington, Seattle; 1993. PMID: 23016163.

Hepatitis C, porphyria cutanea tarda and liver iron: an update. Ryan Caballes F, Sendi H, Bonkovsky HL. Liver Int. 2012 Jul;32(6):880-93. doi: 10.1111/j.1478-3231.2012.02794.x. Epub 2012 Apr 17.

Hereditary Coproporphyria. Bissell DM, Wang B, Cimino T, Lai J. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, eds. GeneReviews. Seattle WA: University of Washington, Seattle; 1993. PMID: 23236641.

Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Singal AK, Kormos-Hallberg C, Lee C, Sadagoparamanujam VM, Grady JJ, Freeman DH Jr, Anderson KE. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1402-9. doi: 10.1016/j.cgh.2012.08.038. Epub 2012 Sep 14.

Porphyrias: prevalence and frequency of testing in a national health care database. Singh A, Pierson K, Wilkinson G, Anderson K. Paper presented at: Annual Meeting of the American Association for the Study of Liver Disease (AASLD); November 9-13, 2012; Boston, MA.

Side chain modification during heme biosynthesis. Phillips JD. In: Kadish KM, Smith KM, Guilard R, eds. Handbook of Porphyrin Science. Vol 16: World Scientific Publishing Company; 2012:283- 337.

The Porphyrias: Cardinal Signs and Diagnosis/Treatment. Desnick RJ. Desnick RJ. The Porphyrias: Cardinal Signs and Diagnosis/Treatment. Paper presented at: American College of Medical Genetics Annual Clinical Genetics Meeting; March 31, 2012; Charlotte, NC.

The porphyrias. Anderson KE. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 24th ed. Philadelphia: Elsevier Saunders; 2012:1363-1371.

The porphyrias: advances in diagnosis and treatment. Balwani M, Desnick RJ. Blood. 2012 Nov 29;120(23):4496-504. doi: 10.1182/blood-2012-05-423186. Epub 2012 Jul 12.

The porphyrias: advances in diagnosis and treatment. Balwani M, Desnick RJ. Hematology Am Soc Hematol Educ Program. 2012;2012:19-27. doi: 10.1182/asheducation-2012.1.19.

A LC-MS/MS method for the specific, sensitive, and simultaneous quantification of 5-aminolevulinic acid and porphobilinogen. Zhang J, Yasuda M, Desnick RJ, Balwani M, Bishop D, Yu C. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Aug 15;879(24):2389-96. doi: 10.1016/j.jchromb.2011.06.034. Epub 2011 Jul 6.

Abnormal mitoferrin-1 expression in patients with erythropoietic protoporphyria. Wang Y, Langer NB, Shaw GC, Yang G, Li L, Kaplan J, Paw BH, Bloomer JR. Exp Hematol. 2011 Jul;39(7):784-94. doi: 10.1016/j.exphem.2011.05.003. Epub 2011 May 11.

CYP1A2*1F and GSTM1 alleles are associated with susceptibility to porphyria cutanea tarda. Wickliffe JK, Abdel-Rahman SZ, Lee C, Kormos-Hallberg C, Sood G, Rondelli CM, Grady JJ, Desnick RJ, Anderson KE. Mol Med. 2011 Mar-Apr;17(3-4):241-7. doi: 10.2119/molmed.2010.00130. Epub 2010 Oct 15. Anderson K. CYP1A2*1F and GSTM1 Alleles Are Associated with Susceptibility to Porphyria Cutanea Tarda. Poster presented at: International Porphyrins & Porphyrias Meeting; April 2011; Cardiff, Wales.

Anderson K. CYP1A2*1F and GSTM1 Alleles Are Associated with Susceptibility to Porphyria Cutanea Tarda. Poster presented at: International Porphyrins & Porphyrias Meeting; April 2011; Cardiff, Wales.

Congenital erythropoietic porphyria: characterization of murine models of the severe common (C73R/C73R) and later-onset genotypes. Bishop DF, Clavero S, Mohandas N, Desnick RJ. Mol Med. 2011;17(7-8):748-56. doi: 10.2119/molmed.2010.00258. Epub 2011 Feb 25.

Discovery of a gene involved in a third bacterial protoporphyrinogen oxidase activity through comparative genomic analysis and functional complementation. Boynton TO, Gerdes S, Craven SH, Neidle EL, Phillips JD, Dailey HA. Appl Environ Microbiol. 2011 Jul;77(14):4795-801. doi: 10.1128/AEM.00171-11. Epub 2011 Jun 3.

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method. Hwang SI, Lee YY, Park JO, Norton HJ, Clemens E, Schrum LW, Bonkovsky HL. Clin Chim Acta. 2011 Nov 20;412(23-24):2241-7. doi: 10.1016/j.cca.2011.08.014. Epub 2011 Aug 16.

Erythropoietic Protoporphyrias: Frequency of Mutations in the Ferrochelatase Gene Causing Autosomal Recessive Erythropoietic Protoporphyria and Mutations in the 5’-Aminolevulinate Synthase 2 Gene Causing X-Linked Protoporphyria (Abstract #1338T). Doheny D, Nazarenko I, Balwani M, Liu L, Naik H, Anderson K, Bissell DM, Bloomer JR, Bonkovsky HL, Kushner JP, Phillips J, Bishop D, Desnick RJ. Paper presented at: 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; October 14, 2011; Montreal, Canada.

Erythropoietic porphyria. Mittal S, Anderson KE. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2011.

Expression and characterization of the ALAS2 carboxy-terminal gain-of-function mutations causing X-linked protoporphyria (Abstract #1157F). Bishop D, Tchaikovskii V, Nazarenko I, Balwani M, Doheny D, Desnick RJ. Paper presented at: 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; October 14, 2011; Montreal, Canada.

Gaucher disease with foamy transformed macrophages and erythrophagocytic activity. Machaczka M, Klimkowska M, Regenthal S, Hägglund H. J Inherit Metab Dis. 2011 Feb;34(1):233-5. doi: 10.1007/s10545-010-9241-0. Epub 2010 Nov 27.

Gaucher disease: when molecular testing and clinical presentation disagree -the novel c.1226A>G(p.N370S)--RecNcil allele. Balwani M, Grace ME, Desnick RJ. J Inherit Metab Dis. 2011 Jun;34(3):789-93. doi: 10.1007/s10545-011-9307-7. Epub 2011 Mar 23.

Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R. Hasanoglu A, Balwani M, Kasapkara CS, Ezgü FS, Okur I, Tümer L, Cakmak A, Nazarenko I, Yu C, Clavero S, Bishop DF, Desnick RJ. J Inherit Metab Dis. 2011 Feb;34(1):225-31. doi: 10.1007/s10545-010-9237-9. Epub 2010 Nov 20.

Heme markedly up-regulates RNA- binding motif protein 24 gene expression in human hepatocytes. Tian Q, Hou W, Steuerwald NM, Schrum LW, Bonkovsky HL. Abstract #895 presented at the Annual Meeting of the American Association for the Study of Liver Diseases. Hepatology. 2011;54(S1):780A.

[Abstract #895 presented at the Annual Meeting of the American Association for the Study of Liver Diseases]

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene. To-Figueras J, Phillips JD, Gonzalez-López JM, Badenas C, Madrigal I, González-Romarís EM, Ramos C, Aguirre JM, Herrero C. Br J Dermatol. 2011 Sep;165(3):499-505. doi: 10.1111/j.1365-2133.2011.10453.x. Epub 2011 Aug 18.

LONP1-dependent breakdown of mitochondrial 5-aminolevulinicacid synthase protein by heme in human liver cells. Tian Q, Hou W, Zheng J, Schrum LW, Bonkovsky HL. Abstract #904 presented at the Annual Meeting of the American Association for the Study of Liver Diseases. Hepatology. 2011;54(S1):785A.

[Abstract #904 presented at the Annual Meeting of the American Association for the Study of Liver Diseases]

Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells. Tian Q, Li T, Hou W, Zheng J, Schrum LW, Bonkovsky HL. J Biol Chem. 2011 Jul 29;286(30):26424-30. doi: 10.1074/jbc.M110.215772. Epub 2011 Jun 9.

Molecular basis of two novel mutations found in type I methemoglobinemia. Lorenzo FRt, Phillips JD, Nussenzveig R, Lingam B, Koul PA, Schrier SL, Prchal JT. Blood Cells Mol Dis. Apr 15 2011;46(4):277-281. PMCID: PMC3075332.

Overview of RDCRN and Porphyrias Consortium Activities. Desnick RJ. Paper presented at: AASLD Annual Meeting; November 6, 2011; San Francisco, CA.

PTF Experience from the Trainee Perspective. Wang B. Paper presented at: AASLD Annual Meeting; November 6, 2011; San Francisco, CA.

Sampangine inhibits heme biosynthesis in both yeast and human. Huang Z, Chen K, Xu T, Zhang J, Li Y, Li W, Agarwal AK, Clark AM, Phillips JD, Pan X. Eukaryot Cell. 2011 Nov;10(11):1536-44. doi: 10.1128/EC.05170-11. Epub 2011 Sep 9.

Structural analysis of heme proteins: implications for design and prediction. Li T, Bonkovsky HL, Guo JT. BMC Struct Biol. 2011 Mar 3;11:13. doi: 10.1186/1472-6807-11-13.

Targeted deletion of the mouse Mitoferrin1 gene: from anemia to protoporphyria. Troadec MB, Warner D, Wallace J, Thomas K, Spangrude GJ, Phillips J, Khalimonchuk O, Paw BH, Ward DM, Kaplan J. Blood. 2011 May 19;117(20):5494-502. doi: 10.1182/blood-2010-11-319483. Epub 2011 Feb 10.

The Escherichia coli protein YfeX functions as a porphyrinogen oxidase, not a heme dechelatase. Dailey HA, Septer AN, Daugherty L, Thames D, Gerdes S, Stabb EV, Dunn AK, Dailey TA, Phillips JD. mBio. 2011 Nov 8;2(6):e00248-11. doi: 10.1128/mBio.00248-11. Print 2011.

The Porphyrias. Phillips JD, Anderson K. In: Lichtman MA, Kaushansky K, Kipps TJ, Prchal JT, Levi MM, eds. Williams Manual of Hematology. 8th ed: McGraw-Hill Professional; 2011.

The cutaneous porphyrias. Anderson K. Paper presented at: AASLD Annual Meeting; November 6, 2011; San Francisco, CA.

The measurement of hepcidin from human urine and serum to study effects of a single dose of oral iron by an optimized LC-MS/MS method. Hwang SI, Lee YY, Park JO, Norton HJ, Clemens E, Schrum LW, Bonkovsky HL. Hepatology. 2011;54(S1):931A. Abstract #1204 presented at Annual Meeting of the American Association for the Study of Liver Diseases.

[Abstract #1204 presented at Annual Meeting of the American Association for the Study of Liver Diseases]

The porphyrias. Anderson K, Lee C, Balwani M, Desnick R. In: Kliegman R, Stanton B, St. Geme J, Schor N, Behrman R, eds. Nelson Textbook of Pediatrics. 19 ed. Philadelphia, PA: Elsevier; 2011.

Uroporphyria in the Cyp1a2-/- mouse. Phillips JD, Kushner JP, Bergonia HA, Franklin MR. Blood Cells Mol Dis. 2011 Dec 15;47(4):249-54. doi: 10.1016/j.bcmd.2011.07.006. Epub 2011 Aug 30.

Zinc protoporphyrin, a novel endogenous HCV NS3-4A protease inhibitor, displays anti-viral activity. Hou W, Tian Q, Lu QL, Schrum LW, Bonkovsky HL. Presidential Poster of Distinction, presented at Annual Meeting of the American Association for the Study of Liver Diseases]. Hepatology. 2011;54(S1):128A-359A.

[Abstract #926 Presidential Poster of Distinction, presented at Annual Meeting of the American Association for the Study of Liver Diseases]

microRNAs: fad or future of liver disease. Lakner AM, Bonkovsky HL, Schrum LW. World J Gastroenterol. May 28 2011;17(20):2536-2542. PMCID: PMC3103811.

AAV8-mediated gene therapy prevents induced biochemical attacks of acute intermittent porphyria and improves neuromotor function. Yasuda M, Bishop DF, Fowkes M, Cheng SH, Gan L, Desnick RJ. Mol Ther. 2010 Jan;18(1):17-22. doi: 10.1038/mt.2009.250. Epub 2009 Oct 27.

Acute intermittent porphyria. Sood G, Anderson KE. Acute intermittent porphyria. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Associations among behavior-related susceptibility factors in porphyria cutanea tarda. Jalil S, Grady JJ, Lee C, Anderson KE. Clin Gastroenterol Hepatol. Mar 2010;8(3):297-302, 302 e291. PMCID: PMC2834813

Clinical manifestations and diagnosis of acute intermittent porphyria. Sood G, Anderson K. In: Rose B, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Congenital erythropoietic porphyria: a novel uroporphyrinogen III synthase branchpoint mutation reveals underlying wild-type alternatively spliced transcripts. Bishop DF, Schneider-Yin X, Clavero S, Yoo HW, Minder EI, Desnick RJ. Blood. 2010 Feb 4;115(5):1062-9. doi: 10.1182/blood-2009-04-218016. Epub 2009 Nov 24.

Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations. Clavero S, Bishop DF, Haskins ME, Giger U, Kauppinen R, Desnick RJ. Hum Mol Genet. 2010 Feb 15;19(4):584-96. doi: 10.1093/hmg/ddp525. Epub 2009 Nov 24.

Feline congenital erythropoietic porphyria: two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation. Clavero S, Bishop DF, Giger U, Haskins ME, Desnick RJ. Mol Med. 2010 Sep-Oct;16(9-10):381-8. doi: 10.2119/molmed.2010.00038. Epub 2010 May 12.

Hepatoerythropoietic porphyria misdiagnosed as child abuse: cutaneous, arthritic, and hematologic manifestations in siblings with a novel UROD mutation. Cantatore-Francis JL, Cohen-Pfeffer J, Balwani M, Kahn P, Lazarus HM, Desnick RJ, Schaffer JV. Arch Dermatol. 2010 May;146(5):529-33. doi: 10.1001/archdermatol.2010.89.

Management of acute intermittent porphyria. Sood G, Anderson K. In: Rose B, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Managing acute porphyrias: practice considerations in inpatient and outpatient settings. Bloomer JR. Medscape Education Gastroenterology. 2010. http://www.medscape.org/viewarticle/730948. Accessed February 28, 2013.

Porphyria cutanea tarda and hepatoerythropoietic porphyria. Singal A, Anderson KE. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Porphyria, ALA-D. Bloomer JR. Rare Disease Database. 2010; http://www.rarediseases.org/rare-disease- information/rare-diseases/byID/324/viewAbstract. Accessed February 29, 2013.

Porphyria, variegate. Anderson KE. Rare Disease Database. 2010; http://www.rarediseases.org/rare-disease- information/rare-diseases/byID/324/viewAbstract. Accessed April 4, 2014.

Porphyria-an overview. Anderson KE. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: a literature review. Gunn GB, Anderson KE, Patel AJ, Gallegos J, Hallberg CK, Sood G, Hatch SS, Sanguineti G. Head Neck. 2010 Aug;32(8):1112-7. doi: 10.1002/hed.21161.

The Porphyrias. Phillips JD, Anderson KE. In: Kaushansky K, Buetler E, Seligsohn U, Lichtman MA, Kipps TJ, Prchal JT, eds. Williams Hematology. 8th ed. New York: McGraw-Hill Medical; 2010:839-863.

Time-of-flight mass spectrometry analysis of the ferroportin-hepcidin binding domain complex for accurate mass confirmation of bioactive hepcidin 25. Crockett DK, Kushnir MM, Phillips JD, Rockwood AL. Clin Chim Acta. 2010 Mar;411(5-6):453-5. doi: 10.1016/j.cca.2009.11.031. Epub 2009 Dec 3.

Variegate porphyria. Singal A, Anderson KE. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2010.

Zinc mesoporphyrin induces rapid proteasomal degradation of hepatitis C nonstructural 5A protein in human hepatoma cells. Hou W, Tian Q, Zheng J, Bonkovsky HL. Gastroenterology. 2010 May;138(5):1909-19. doi: 10.1053/j.gastro.2009.11.001. Epub 2009 Nov 10.

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives. Badenas C, To-Figueras J, Phillips JD, Warby CA, Muñoz C, Herrero C. Clin Genet. 2009 Apr;75(4):346-53. doi: 10.1111/j.1399-0004.2009.01153.x.

Acute intermittent porphyria. Anderson K, Sood G. Anderson K, Sood G. Acute intermittent porphyria. Best Practice. London, UK: BMJ Publishing Group; 2008.

Porphyria Cutanea Tarda. Sood G, Anderson K. Best Practice. London, UK: BMJ Publishing Group; 2008.

Porphyrias. Sood G, Anderson K. In: Crowther M, Ginsberg J, Schunemann H, Meyer R, Lottenberg R, eds. Evidence-Based Hematology. United Kingdom: Blackwell Publishing Ltd; 2008:229-237.

The Porphyrias. Phillips JD, Kushner JP. In: Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE, eds. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia: Saunders 2008.

Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation. Labrosse R, Boufaied I, Bourdin B, Gona S, Randolph HE, Logan BR, Bourbonnais S, Berthe C, Chan W, Buckley RH, Parrott RE, Cuvelier GDE, Kapoor N, Chandra S, Dávila Saldaña BJ, Eissa H, Goldman FD, Heimall J, O'Reilly R, Chaudhury S, Kolb EA, Shenoy S, Griffith LM, Pulsipher M, Kohn DB, Notarangelo LD, Pai SY, Cowan MJ, Dvorak CC, Haddad É, Puck JM, Barreiro LB, Decaluwe H. J Allergy Clin Immunol. 2023 Jan;151(1):260-271. doi: 10.1016/j.jaci.2022.08.004. Epub 2022 Aug 17.

Genotype, oxidase status, and preceding infection or autoinflammation do not affect allogeneic HCT outcomes for CGD. Leiding JW, Arnold DE, Parikh S, Logan B, Marsh RA, Griffith LM, Wu R, Kidd S, Mallhi K, Chellapandian D, Si Lim SJ, Grunebaum E, Falcone EL, Murguia-Favela L, Grossman D, Prasad VK, Heimall JR, Touzot F, Burroughs LM, Bleesing J, Kapoor N, Dara J, Williams O, Kapadia M, Oshrine BR, Bednarski JJ, Rayes A, Chong H, Cuvelier GDE, Forbes Satter LR, Martinez C, Vander Lugt MT, Yu LC, Chandrakasan S, Joshi A, Prockop SE, Dávila Saldaña BJ, Aquino V, Broglie LA, Ebens CL, Madden LM, DeSantes K, Milner J, Rangarajan HG, Shah AJ, Gillio AP, Knutsen AP, Miller HK, Moore TB, Graham P, Bauchat A, Bunin NJ, Teira P, Petrovic A, Chandra S, Abdel-Azim H, Dorsey MJ, Birbrayer O, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM. Blood. 2023 Dec 14;142(24):2105-2118. doi: 10.1182/blood.2022019586. PMID: 37562003

Chronic granulomatous disease (CGD) is a type of primary immunodeficiency characterized by life-threatening infections and inflammation. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD. However, questions remain about patient selection and how active disease impacts transplant outcomes.

In this study, researchers investigated outcomes of allogeneic (donor) HCT in patients with CGD. The team performed an analysis of 391 participants treated either with or without HCT, following outcomes over several years.

Results show that HCT quickly and durably resolves CGD symptoms, lowers the burden of the disease, and has excellent survival rates. Patients with active inflammation or infection are candidates for HCT. To avoid complications from the development of additional medical conditions, authors note that HCT should be considered early in patients with CGD.

Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT. Schuetz C, Gerke J, Ege M, Walter J, Kusters M, Worth A, Kanakry JA, Dimitrova D, Wolska-Kuśnierz B, Chen K, Unal E, Karakukcu M, Pashchenko O, Leiding J, Kawai T, Amrolia PJ, Berghuis D, Buechner J, Buchbinder D, Cowan MJ, Gennery AR, Güngör T, Heimall J, Miano M, Meyts I, Morris EC, Rivière J, Sharapova SO, Shaw PJ, Slatter M, Honig M, Veys P, Fischer A, Cavazzana M, Moshous D, Schulz A, Albert MH, Puck JM, Lankester AC, Notarangelo LD, Neven B. Blood. 2023 Feb 16;141(7):713-724. doi: 10.1182/blood.2022017667.

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium. Thakar MS, Logan BR, Puck JM, Dunn EA, Buckley RH, Cowan MJ, O'Reilly RJ, Kapoor N, Satter LF, Pai SY, Heimall J, Chandra S, Ebens CL, Chellapandian D, Williams O, Burroughs LM, Saldana BD, Rayes A, Madden LM, Chandrakasan S, Bednarski JJ 2nd, DeSantes KB, Cuvelier GDE, Teira P, Gillio AP, Eissa H, Knutsen AP, Goldman FD, Aquino VM, Shereck EB, Moore TB, Caywood EH, Lugt MTV, Rozmus J, Broglie L, Yu LC, Shah AJ, Andolina JR, Liu X, Parrott RE, Dara J, Prockop S, Martinez CA, Kapadia M, Jyonouchi SC, Sullivan KE, Bleesing JJ, Chaudhury S, Petrovic A, Keller MD, Quigg TC, Parikh S, Shenoy S, Seroogy C, Rubin T, Decaluwe H, Routes JM, Torgerson TR, Leiding JW, Pulsipher MA, Kohn DB, Griffith LM, Haddad E, Dvorak CC, Notarangelo LD.. Lancet. 2023 Jul 8;402(10396):129-140. doi: 10.1016/S0140-6736(23)00731-6. Epub 2023 Jun 20. PMID: 37352885

Severe combined immunodeficiency (SCID) is a severe form of primary immune deficiency characterized by extreme weakness or absence of immune system function. SCID is fatal, unless durable adaptive immunity is established—most commonly through allogeneic hematopoietic cell transplantation (HCT).

In this study, researchers from the Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades. The team focused on the effects of population-based newborn screening for SCID, analyzing transplantation-related data from children with SCID treated at 34 PIDTC sites.

Results show that population-based newborn screening has helped to identify infants with SCID early in life, increasing the likelihood of prompt HCT prior to the development of serious infections. Authors state that public health programs worldwide can benefit from this demonstration of the value of newborn screening for SCID.

A Spot of Good News: Israeli Experience With SCID Newborn Screening. Puck JM. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2732-2733. doi: 10.1016/j.jaip.2022.08.014.

Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH). Kumar D, Rostad CA, Jaggi P, Villacis Nunez DS, Prince C, Lu A, Hussaini L, Nguyen TH, Malik S, Ponder LA, Shenoy SPV, Anderson EJ, Briones M, Sanz I, Prahalad S, Chandrakasan S. J Allergy Clin Immunol. 2022 May;149(5):1592-1606.e16. doi: 10.1016/j.jaci.2022.02.028. Epub 2022 Mar 15. PMID: 35304157; PMCID: PMC8923010.

Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy. Arnold DE, Chellapandian D, Parikh S, Mallhi K, Marsh RA, Heimall JR, Grossman D, Chitty-Lopez M, Murguia-Favela L, Gennery AR, Boulad F, Arbuckle E, Cowan MJ, Dvorak CC, Griffith LM, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson T, Kang EM, Malech HL, Leiding JW. J Clin Immunol. 2022 Jul;42(5):1026-1035. doi: 10.1007/s10875-022-01261-1. Epub 2022 Apr 21. PMID: 35445907; PMCID: PMC9022412.

HSCT using carrier donors for CD40L deficiency results in excellent immune function and higher CD40L expression in cTfh. Chandrakasan S, Chandra S, Prince C, Kobrynski LJ, Lucas L, Patel K, Walter J, Buckley RH, Meisel R, Ghosh S, Parikh SH. Blood Adv. 2022 Jun 28;6(12):3751-3755. doi: 10.1182/bloodadvances.2021006905. PMID: 35443026.

PIDTC: HSCT using carrier donors for CD40L deficiency results in excellent immune function and higher CD40L expression in cTfh CD40 ligand (CD40L) deficiency is a rare X-linked immunodeficiency disorder that leads to recurrent bacterial infections. Not much is known about the immune status of CD40L-deficient carriers, or possible outcomes of hematopoietic stem cell transplantation (HSCT) using these carriers as donors for CD40L-deficient patients. In this study, researchers evaluated the immune profiles of 7 carriers—including 4 who acted as HSCT donors for family members with CD40L deficiency—and characterized their HSCT outcomes. Results show that most carriers with CD40L deficiency have a normal immune profile with differential high CD40L expression in circulating T follicular helper (cTfh) cells, which are critical for immune response. The team also reported excellent long-term immune reconstitution in CD40L-deficient patients after HSCT using carrier donors. Authors state that HSCT using X-linked carriers seems to be safe and results in excellent outcomes. Authors also note that this decision should be individualized and driven by the biology of the disease. Note: First author Shanmuganathan Chandrakasan, MD, received the 2017 PIDTC Fellowship Award.

Human JAK1 gain of function causes dysregulated myelopoeisis and severe allergic inflammation. Biggs CM, Cordeiro-Santanach A, Prykhozhij SV, Deveau AP, Lin Y, Del Bel KL, Orben F, Ragotte RJ, Saferali A, Mostafavi S, Dinh L, Dai D, Weinacht KG, Dobbs K, Ott de Bruin L, Sharma M, Tsai K, Priatel JJ, Schreiber RA, Rozmus J, Hosking MC, Shopsowitz KE, McKinnon ML, Vercauteren S, Seear M, Notarangelo LD, Lynn FC, Berman JN, Turvey SE. JCI Insight. 2022 Dec 22;7(24):e150849. doi: 10.1172/jci.insight.150849. PMID: 36546480; PMCID: PMC9869972.

Primary atopic disorders are a group of rare inherited conditions that cause severe allergic disease. Each of these disorders is monogenic—controlled by a single gene—and causes its own unique condition. Studying primary atopic disorders teaches us about the genes and biology underlying allergic disease. We can then apply these lessons learned to identify better treatments for both primary atopic disorders and common allergic conditions. 

In this study, researchers explored a germline gain-of-function variant in the JAK1 gene, which is a cause of severe atopy (the genetic predisposition to developing allergic diseases) and eosinophilia (an unusually high number of a type of white blood cell called eosinophils). To investigate how enhanced JAK1 signaling promotes allergic inflammation, the team performed RNA sequencing of human whole blood, induced pluripotent stem cells, and zebrafish carrying the JAK1 gain-of-function variant.

Results reveal that the JAK1 gain-of-function variant causes dysregulated myelopoiesis (production of blood cells in bone marrow) and severe allergic inflammation. For two pediatric patients carrying the variant, researchers found that long-term treatment with the drug ruxolitinib remarkably improved their growth, eosinophilia, and clinical features of allergic inflammation. Authors note that this study highlights the role of JAK1 signaling in atopic immune dysregulation, as well as the clinical impact of medications inhibiting JAK1 and JAK2 in treating eosinophilic and allergic disease. 

Lentiviral Gene Therapy for Artemis-Deficient SCID. Cowan MJ, Yu J, Facchino J, Fraser-Browne C, Sanford U, Kawahara M, Dara J, Long-Boyle J, Oh J, Chan W, Chag S, Broderick L, Chellapandian D, Decaluwe H, Golski C, Hu D, Kuo CY, Miller HK, Petrovic A, Currier R, Hilton JF, Punwani D, Dvorak CC, Malech HL, McIvor RS, Puck JM. N Engl J Med. 2022 Dec 22;387(25):2344-2355. doi: 10.1056/NEJMoa2206575. PMID: 36546626.

Artemis-deficient severe combined immunodeficiency (ART-SCID) is a rare form of primary immune deficiency caused by mutations in the DCLRE1C gene. Allogeneic hematopoietic-cell transplantation, the standard treatment for patients with SCID, can effectively treat other forms of SCID. However, ART-SCID does not respond well to this therapy, highlighting the need for alternative treatments. In this study, researchers evaluated the effects of transfusing lentiviral gene-corrected autologous CD34+ bone marrow cells in 10 infants with newly diagnosed ART-SCID. The team followed these patients for a median of 31.2 months. Findings showed that infusion of these bone marrow cells—after conditioning with a low dose of the chemotherapy drug busulfan—resulted in genetically corrected and functional T and B cells. Authors state that larger studies of longer duration are needed to further assess the safety and efficacy of this approach.

Outcomes Following Treatment for Adenosine Deaminase Deficient Severe Combined Immunodeficiency: A Report from the PIDTC. Cuvelier GDE, Logan BR, Prockop S, Buckley RH, Kuo CY, Griffith LM, Liu X, Yip A, Hershfield M, Ayoub P, Moore TB, Dorsey M, O'Reilly RJ, Kapoor N, Pai SY, Kapadia M, Ebens CL, Forbes Satter LR, Burroughs L, Petrovic A, Chellapandian D, Heimall J, Shyr D, Rayes A, Bednarski JJ, Chandra S, Chandrakasan S, Gilio AP, Madden LM, Quigg TC, Caywood EH, Dávila Saldaña BJ, DeSantes K, Eissa H, Goldman FD, Rozmus J, Shah A, Vander Lugt MT, Thakar MS, Parrott RE, Martinez CA, Leiding JW, Torgerson TR, Pulsipher MA, Notarangelo LD, Cowan MJ, Dvorak CC, Haddad E, Puck JM, Kohn DB. Blood. 2022 Jun 7:blood.2022016196. doi: 10.1182/blood.2022016196. Epub ahead of print. PMID: 35671392.

Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution. Delmonte OM, Castagnoli R, Yu J, Dvorak CC, Cowan MJ, Dávila Saldaña BJ, De Ravin SS, Mamcarz E, Chang CK, Daley SR, Griffith LM, Notarangelo LD, Puck JM. J Allergy Clin Immunol. 2022 Mar;149(3):1113-1119. doi: 10.1016/j.jaci.2021.07.029. Epub 2021 Aug 9. PMID: 34384841; PMCID: PMC9132846.

Severe combined immunodeficiency (SCID) is a form of primary immune deficiency characterized by impaired T-cell development. Following hematopoietic cell transplantation (HCT) for SCID, development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery. In this study, researchers investigated whether longitudinal analysis of the TRB repertoire would accurately describe T-cell receptor diversity and composition following HCT for SCID. Using high-throughput sequencing, the team studied the TRB repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s). Results showed that TRB repertoire after HCT for SCID provides a quantitative and qualitative measure of diversity of T-cell reconstitution. Authors note that this analysis can help identify patients who may require a second intervention.

Recommendations for uniform definitions used in newborn screening for severe combined immunodeficiency. Blom M, Zetterström RH, Stray-Pedersen A, Gilmour K, Gennery AR, Puck JM, van der Burg M. J Allergy Clin Immunol. 2022 Apr;149(4):1428-1436. doi: 10.1016/j.jaci.2021.08.026. Epub 2021 Sep 16.

T-follicular helper cell expansion and chronic T-cell activation are characteristic immune anomalies in Evans syndrome. Kumar D, Prince C, Bennett CM, Briones M, Lucas L, Russell A, Patel K, Chonat S, Graciaa S, Edington H, White MH, Kobrynski L, Abdalgani M, Parikh S, Chandra S, Bleesing J, Marsh R, Park S, Waller EK, Prahalad S, Chandrakasan S. Blood. 2022 Jan 20;139(3):369-383. doi: 10.1182/blood.2021012924.

The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions. Dvorak CC, Haddad E, Heimall J, Dunn E, Buckley RH, Kohn DB, Cowan MJ, Pai SY, Griffith LM, Cuvelier GDE, Eissa H, Shah AJ, O'Reilly RJ, Pulsipher MA, Wright NAM, Abraham RS, Satter LF, Notarangelo LD, Puck JM. J Allergy Clin Immunol. 2022 Nov 28:S0091-6749(22)01479-8. doi: 10.1016/j.jaci.2022.10.022. Epub ahead of print. PMID: 36456361.

Severe combined immunodeficiency (SCID) is a severe form of primary immune deficiency characterized by extreme weakness or absence of immune system function, manifesting at birth. SCID results from abnormalities in responses of both T cells and B cells, which are types of white blood cells needed for immune system function. In 2014, the Primary Immune Deficiency Treatment Consortium (PIDTC) published criteria used to qualify patients for enrollment in their prospective and retrospective studies of SCID. In this article, researchers update the criteria, incorporating contemporary diagnostic approaches. These include increased availability of gene sequencing, as well as widespread population-based newborn screening for SCID. This article proposes that these criteria be used to establish a diagnosis of SCID in 2022. Authors state that the new definitions allow for more precise categorization of patients with SCID and atypical or leaky SCID. However, the definitions do not imply a preferred treatment strategy.

The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions. Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai SY, Kapoor N, Satter LF, Buckley RH, O'Reilly RJ, Chandra S, Bednarski JJ, Williams O, Rayes A, Moore TB, Ebens CL, Davila Saldana BJ, Petrovic A, Chellapandian D, Cuvelier GDE, Vander Lugt MT, Caywood EH, Chandrakasan S, Eissa H, Goldman FD, Shereck E, Aquino VM, Desantes KB, Madden LM, Miller HK, Yu L, Broglie L, Gillio A, Shah AJ, Knutsen AP, Andolina JP, Joshi AY, Szabolcs P, Kapadia M, Martinez CA, Parrot RE, Sullivan KE, Prockop SE, Abraham RS, Thakar MS, Leiding JW, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Puck JM. J Allergy Clin Immunol. 2022 Nov 28:S0091-6749(22)01478-6. doi: 10.1016/j.jaci.2022.10.021. Epub ahead of print. PMID: 36456360.

In 2014, the Primary Immune Deficiency Treatment Consortium (PIDTC) published criteria developed for the diagnosis and classification of severe combined immunodeficiency (SCID) patients enrolling in their protocols. Since then, newborn screening for SCID has become increasingly common, as well as more rapid and less costly genetic sequencing. In light of these advances, the PIDTC updated their definitions in 2022. In this study, researchers compared the performance of the original versus the updated definitions. The team analyzed 379 patients who were proposed for enrollment in a PIDTC prospective protocol that follows SCID patients longitudinally, focusing on the ability to distinguish patients with various subtypes of SCID. Results showed that the 2022 definitions described SCID and its subtypes more precisely than the 2014 definitions. Authors state that these updates can facilitate improved analyses of SCID characteristics and outcomes.

Comparative Survival Analysis of Immunomodulatory Therapy for Coronavirus Disease 2019 Cytokine Storm. Narain S, Stefanov DG, Chau AS, Weber AG, Marder G, Kaplan B, Malhotra P, Bloom O, Liu A, Lesser ML, Hajizadeh N; Northwell COVID-19 Research Consortium. Chest. 2021 Mar;159(3):933-948. doi: 10.1016/j.chest.2020.09.275. Epub 2020 Oct 17.

Establishing Newborn Screening for SCID in the USA; Experience in California. Puck JM, Gennery AR. Int J Neonatal Screen. 2021 Oct 31;7(4):72. doi: 10.3390/ijns7040072. PMID: 34842619; PMCID: PMC8628983.

Expectations and experience: Parent and patient perspectives regarding treatment for Severe Combined Immunodeficiency (SCID). Smith H, Scalchunes C, Cowan MJ, Puck J, Heimall J. Clin Immunol. 2021 Aug;229:108778. doi: 10.1016/j.clim.2021.108778. Epub 2021 Jun 16. PMID: 34144198; PMCID: PMC8559521.

Severe combined immunodeficiency (SCID) is a group of rare disorders caused by mutations in different genes involved in the development and function of infection-fighting immune cells. Infants with SCID are treated with hematopoietic cell transplantation (HCT, also called bone marrow transplantation or stem cell transplantation) or gene therapy (an experimental form of treatment that uses transfer of genetic material into the cell of a patient to treat or stop disease). To test parent and patient expectations and experience with these treatments, researchers distributed 151 surveys to families of patients with SCID treated with HCT or gene therapy. They found that 37% of respondents expected the therapy would lead to a “cure” and 43% expected it would last a lifetime. Researchers found that varying interpretations of the word “cure” led to misunderstandings regarding the need for continued medical evaluations and therapies. They concluded that clear communication about the importance of lifelong follow-up, regardless of treatment outcome, is needed to optimize health and quality of life.

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers. Dorsey MJ, Wright NAM, Chaimowitz NS, Dávila Saldaña BJ, Miller H, Keller MD, Thakar MS, Shah AJ, Abu-Arja R, Andolina J, Aquino V, Barnum JL, Bednarski JJ, Bhatia M, Bonilla FA, Butte MJ, Bunin NJ, Chandra S, Chaudhury S, Chen K, Chong H, Cuvelier GDE, Dalal J, DeFelice ML, DeSantes KB, Forbes LR, Gillio A, Goldman F, Joshi AY, Kapoor N, Knutsen AP, Kobrynski L, Lieberman JA, Leiding JW, Oshrine B, Patel KP, Prockop S, Quigg TC, Quinones R, Schultz KR, Seroogy C, Shyr D, Siegel S, Smith AR, Torgerson TR, Vander Lugt MT, Yu LC, Cowan MJ, Buckley RH, Dvorak CC, Griffith LM, Haddad E, Kohn DB, Logan B, Notarangelo LD, Pai SY, Puck J, Pulsipher MA, Heimall J. J Clin Immunol. 2021 Jan;41(1):38-50. doi: 10.1007/s10875-020-00865-9. Epub 2020 Oct 2.

SCID newborn screening: What we've learned. Currier R, Puck JM. J Allergy Clin Immunol. 2021 Feb;147(2):417-426. doi: 10.1016/j.jaci.2020.10.020.

Successful SCID gene therapy in infant with disseminated BCG. Maron G, Kaste S, Bahrami A, Neel M, Malech HL, Puck JM, Cowan MJ, Gottschalk S, Mamcarz E. J Allergy Clin Immunol Pract. 2021 Feb;9(2):993-995.e1. doi: 10.1016/j.jaip.2020.09.004. Epub 2020 Sep 16.

T Cell-Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis (HLH) Occurs in Non-Asians and Is Associated with a T Cell Activation State that Is Comparable to Primary HLH. Shamriz O, Kumar D, Shim J, Briones M, Quarmyne MO, Chonat S, Lucas L, Edington H, White MH, Mahajan A, Park S, Chandrakasan S. J Clin Immunol. 2021 Oct;41(7):1582-1596. doi: 10.1007/s10875-021-01073-9. Epub 2021 Jun 26.

The Longitudinal Immune Response to Coronavirus Disease 2019: Chasing the Cytokine Storm. Chau AS, Weber AG, Maria NI, Narain S, Liu A, Hajizadeh N, Malhotra P, Bloom O, Marder G, Kaplan B. Arthritis Rheumatol. 2021 Jan;73(1):23-35. doi: 10.1002/art.41526. Epub 2020 Dec 1.

Unknown cytomegalovirus serostatus in primary immunodeficiency disorders: A new category of transplant recipients. Forlanini F, Dara J, Dvorak CC, Cowan MJ, Puck JM, Dorsey MJ. Transpl Infect Dis. 2021 Apr;23(2):e13504. doi: 10.1111/tid.13504. Epub 2020 Nov 29.

When Screening for Severe Combined Immunodeficiency (SCID) with T Cell Receptor Excision Circles Is Not SCID: a Case-Based Review. Buchbinder D, Walter JE, Butte MJ, Chan WY, Chitty Lopez M, Dimitriades VR, Dorsey MJ, Nugent DJ, Puck JM, Singh J, Collins CA. J Clin Immunol. 2021 Feb;41(2):294-302. doi: 10.1007/s10875-020-00931-2. Epub 2021 Jan 7. PMID: 33411155; PMCID: PMC8179373.

Artificial thymic organoids represent a reliable tool to study T-cell differentiation in patients with severe T-cell lymphopenia. Bosticardo M, Pala F, Calzoni E, Delmonte OM, Dobbs K, Gardner CL, Sacchetti N, Kawai T, Garabedian EK, Draper D, Bergerson JRE, DeRavin SS, Freeman AF, Güngör T, Hartog N, Holland SM, Kohn DB, Malech HL, Markert ML, Weinacht KG, Villa A, Seet CS, Montel-Hagen A, Crooks GM, Notarangelo LD. Blood Adv. 2020 Jun 23;4(12):2611-2616. doi: 10.1182/bloodadvances.2020001730.

Diagnostic assay to assist clinical decisions for unclassified severe combined immune deficiency. Bifsha P, Leiding JW, Pai SY, Colamartino ABL, Hartog N, Church JA, Oshrine BR, Puck JM, Markert ML, Haddad E. Blood Adv. 2020 Jun 23;4(12):2606-2610. doi: 10.1182/bloodadvances.2020001736.

Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report. Burroughs LM, Petrovic A, Brazauskas R, Liu X, Griffith LM, Ochs HD, Bleesing JJ, Edwards S, Dvorak CC, Chaudhury S, Prockop SE, Quinones R, Goldman FD, Quigg TC, Chandrakasan S, Smith AR, Parikh S, Dávila Saldaña BJ, Thakar MS, Phelan R, Shenoy S, Forbes LR, Martinez C, Chellapandian D, Shereck E, Miller HK, Kapoor N, Barnum JL, Chong H, Shyr DC, Chen K, Abu-Arja R, Shah AJ, Weinacht KG, Moore TB, Joshi A, DeSantes KB, Gillio AP, Cuvelier GDE, Keller MD, Rozmus J, Torgerson T, Pulsipher MA, Haddad E, Sullivan KE, Logan BR, Kohn DB, Puck JM, Notarangelo LD, Pai SY, Rawlings DJ, Cowan MJ. Blood. 2020 Jun 4;135(23):2094-2105. doi: 10.1182/blood.2019002939.

We are excited to share the results of our paper, “Excellent Outcomes Following Hematopoietic Cell Transplantation for Wiskott-Aldrich Syndrome: A PIDTC Report” that was recently published in the medical journal, Blood in June 2020. PIDTC 6904 is a clinical research study of the outcomes of patients with Wiskott-Aldrich syndrome who have undergone transplant at PIDTC centers. The study was open at over 42 PIDTC centers and has enrolled over 300 patients across North America! Patients with Wiskott-Aldrich syndrome (WAS) are at increased risk for lifethreatening infections, bleeding complications, and autoimmune problems due to their disease. Transplant is the primary curative approach, with the goal of correcting the underlying immune and platelet problems. In our first paper, we did a retrospective study of 129 patients with WAS who had undergone transplantation at PIDTC centers from 2005-2015. Importantly, we found excellent survival (>90%) following transplant regardless of what type of donor (sibling or unrelated donor) or hematopoietic cell source (bone marrow, peripheral blood, or cord blood) was used. Age at transplant remained a key factor with better survival in patients who were younger than age 5 years at the time of transplant versus those who were older. This finding highlights the importance of performing the transplant early in the course of the disease before the patient develops complications which can make it more difficult to do the transplant safely. We also looked at how the type of conditioning the patient received (full intensity versus reduced intensity) affects transplant outcomes. We did not find a difference in survival; however, we did find a difference in engraftment (how well the transplant took) with higher donor cell percentage in patients who received Busulfan-based conditioning regimens versus other reduced intensity regimens. Higher donor cell percentage in turn was needed to correct the platelet count. Which conditioning regimen is best remains an unanswered question that we are hoping to study further in our next paper, which includes more retrospective cases and data from patients who enrolled in our prospective natural history study. Additional studies are also needed that look at the long-term outcomes of patients who have undergone transplant. This study highlights the importance of centers working together to advance patient care, particularly for patients with rare diseases. The PIDTC is a consortium of 43 centers in North America whose shared goal is to improve the outcomes of patients with rare, life threatening, inherited disorders of the immune system ISSUE 12 |WINTER 2020| PAGE 10 including WAS, severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), and primary immune regulatory disorders. We would like to thank all the patients and families who made this work possible!

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey. Chan AY, Leiding JW, Liu X, Logan BR, Burroughs LM, Allenspach EJ, Skoda-Smith S, Uzel G, Notarangelo LD, Slatter M, Gennery AR, Smith AR, Pai SY, Jordan MB, Marsh RA, Cowan MJ, Dvorak CC, Craddock JA, Prockop SE, Chandrakasan S, Kapoor N, Buckley RH, Parikh S, Chellapandian D, Oshrine BR, Bednarski JJ, Cooper MA, Shenoy S, Davila Saldana BJ, Forbes LR, Martinez C, Haddad E, Shyr DC, Chen K, Sullivan KE, Heimall J, Wright N, Bhatia M, Cuvelier GDE, Goldman FD, Meyts I, Miller HK, Seidel MG, Vander Lugt MT, Bacchetta R, Weinacht KG, Andolina JR, Caywood E, Chong H, de la Morena MT, Aquino VM, Shereck E, Walter JE, Dorsey MJ, Seroogy CM, Griffith LM, Kohn DB, Puck JM, Pulsipher MA, Torgerson TR. Front Immunol. 2020 Feb 21;11:239. doi: 10.3389/fimmu.2020.00239. eCollection 2020.

Primary Immune Regulatory Disorders (PIRD) are a new group of conditions where the immune system is not responding and regulating the immune response appropriately. These diseases can affect multiple organs and are often cared for by many different specialists. Thus, little is known about the natural history of this group of diseases and the ideal treatment for PIRD. To help us better understand this group of disorders, we conducted a survey among 30 centers in the PIDTC and 3 centers in Europe to look at the outcome of patients that have been transplanted for PIRD. We collected data on 226 patients who had received a transplant for a PIRD condition. Roughly 75% of patients had a genetic diagnosis and a quarter did not. Most patients developed symptoms within a year of age. Almost all organ systems were affected, and many patients had multiple affected organs. The most common problems included gastrointestinal issues, blood count issues (autoimmune cytopenias), and rashes. The main reason for transplant was autoimmune problems (41%), and the next most common reason was infections (26%). Roughly a quarter of the patients had multiple reasons for transplant. Nearly all of the patients were transplanted before 18 years of age, and approximately a quarter of the patients were transplanted before a year of age. More than half of patients had resolution of their symptoms, and the overall 5-year survival for transplanted PIRD patients was 67%. This is the first study to look at transplant for PIRD and highlights a need to improve our understanding of this condition and what therapies are ideal for treating this group. This survey served as the basis for the development of the 6906 protocol which will focus on studying the natural history of PIRD to improve survival for patients with this condition.

Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused by UNC13D Genetic Defects. Takushi SE, Paik NY, Fedanov A, Prince C, Doering CB, Spencer HT, Chandrakasan S. Hum Gene Ther. 2020 Jun;31(11-12):626-638. doi: 10.1089/hum.2019.329.

Multiplexed Functional Assessment of Genetic Variants in CARD11. Meitlis I, Allenspach EJ, Bauman BM, Phan IQ, Dabbah G, Schmitt EG, Camp ND, Torgerson TR, Nickerson DA, Bamshad MJ, Hagin D, Luthers CR, Stinson JR, Gray J, Lundgren I, Church JA, Butte MJ, Jordan MB, Aceves SS, Schwartz DM, Milner JD, Schuval S, Skoda-Smith S, Cooper MA, Starita LM, Rawlings DJ, Snow AL, James RG. Am J Hum Genet. 2020 Nov 12:S0002-9297(20)30373-6. doi: 10.1016/j.ajhg.2020.10.015. Epub ahead of print. PMID: 33202260. PMCID: PMC7820631.

There has been a rapid increase in the availability and utilization of genetic testing in medicine, but the interpretation of these genetic results is often lagging. Patients often get reports labeling variants of “uncertain significance”, which should not be used for medical decision making. This hinders precision medicine. There are many pieces of data that clinicians and geneticists use to interpret variants as either benign or disease-causing including functional testing. Often this time-consuming process follows variant identification and delays treatment. In this study, we focused on a novel approach to simultaneously screen the functional effect of a large number of variants in the gene CARD11, an adaptor protein that expresses blocking or gain-offunction variants associated with distinct immunodeficiencies. We used genome editing to make a population of cells with all possible genetic changes at the same time to functionally screen them to provide a database to provide up front predictions. This information can now be utilized together with family history, clinical symptoms and other laboratory testing to aid in diagnosis. We generated functional scores for 2,542 coding and 38 noncoding variants of CARD11 and applied our predictions to new patients with novel mutations and compared to traditional methods. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency ISSUE 12 |WINTER 2020| PAGE 6 found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.

Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series. Weber AG, Chau AS, Egeblad M, Barnes BJ, Janowitz T. medRxiv. 2020 May 15:2020.05.13.20087734. doi: 10.1101/2020.05.13.20087734. Preprint.

Primary immune regulatory disorders: a growing universe of immune dysregulation. Chan AY, Torgerson TR. Curr Opin Allergy Clin Immunol. 2020 Dec;20(6):582-590. doi: 10.1097/ACI.0000000000000689.

Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT. Marsh RA, Leiding JW, Logan BR, Griffith LM, Arnold DE, Haddad E, Falcone EL, Yin Z, Patel K, Arbuckle E, Bleesing JJ, Sullivan KE, Heimall J, Burroughs LM, Skoda-Smith S, Chandrakasan S, Yu LC, Oshrine BR, Cuvelier GDE, Thakar MS, Chen K, Teira P, Shenoy S, Phelan R, Forbes LR, Chellapandian D, Dávila Saldaña BJ, Shah AJ, Weinacht KG, Joshi A, Boulad F, Quigg TC, Dvorak CC, Grossman D, Torgerson T, Graham P, Prasad V, Knutsen A, Chong H, Miller H, de la Morena MT, DeSantes K, Cowan MJ, Notarangelo LD, Kohn DB, Stenger E, Pai SY, Routes JM, Puck JM, Kapoor N, Pulsipher MA, Malech HL, Parikh S, Kang EM; submitted on behalf of the Primary Immune Deficiency Treatment Consortium. J Clin Immunol. 2019 Oct;39(7):653-667. doi: 10.1007/s10875-019-00659-8. Epub 2019 Aug 2.

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, Notarangelo LD, Grunebaum E. J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5.

Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study. Ferrua F, Galimberti S, Courteille V, Slatter MA, Booth C, Moshous D, Neven B, Blanche S, Cavazzana M, Laberko A, Shcherbina A, Balashov D, Soncini E, Porta F, Al-Mousa H, Al-Saud B, Al-Dhekri H, Arnaout R, Formankova R, Bertrand Y, Lange A, Smart J, Wolska-Kusnierz B, Aquino VM, Dvorak CC, Fasth A, Fouyssac F, Heilmann C, Hoenig M, Schuetz C, Kelečić J, Bredius RGM, Lankester AC, Lindemans CA, Suarez F, Sullivan KE, Albert MH, Kałwak K, Barlogis V, Bhatia M, Bordon V, Czogala W, Alonso L, Dogu F, Gozdzik J, Ikinciogullari A, Kriván G, Ljungman P, Meyts I, Mustillo P, Smith AR, Speckmann C, Sundin M, Keogh SJ, Shaw PJ, Boelens JJ, Schulz AS, Sedlacek P, Veys P, Mahlaoui N, Janda A, Davies EG, Fischer A, Cowan MJ, Gennery AR; SCETIDE, PIDTC, EBMT & ESID IEWP. J Allergy Clin Immunol. 2019 Jun;143(6):2238-2253. doi: 10.1016/j.jaci.2018.12.1010. Epub 2019 Jan 17.

Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. N Engl J Med. 2019 Apr 18;380(16):1525-1534. doi: 10.1056/NEJMoa1815408.

Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency. Dvorak CC, Long-Boyle J, Dara J, Melton A, Shimano KA, Huang JN, Puck JM, Dorsey MJ, Facchino J, Chang CK, Cowan MJ. Biol Blood Marrow Transplant. 2019 Jul;25(7):1355-1362. doi: 10.1016/j.bbmt.2019.03.008. Epub 2019 Mar 12.

Newborn Screening for Severe Combined Immunodeficiency and T-cell Lymphopenia in California, 2010-2017. Amatuni GS, Currier RJ, Church JA, Bishop T, Grimbacher E, Nguyen AA, Agarwal-Hashmi R, Aznar CP, Butte MJ, Cowan MJ, Dorsey MJ, Dvorak CC, Kapoor N, Kohn DB, Markert ML, Moore TB, Naides SJ, Sciortino S, Feuchtbaum L, Koupaei RA, Puck JM. Pediatrics. 2019 Feb;143(2):e20182300. doi: 10.1542/peds.2018-2300.

Newborn Screening for Severe Combined Immunodeficiency in the United States: Lessons Learned. Dorsey MJ, Puck JM. Immunol Allergy Clin North Am. 2019 Feb;39(1):1-11. doi: 10.1016/j.iac.2018.08.002. Epub 2018 Nov 1.

Newborn screening for severe combined immunodeficiency and T-cell lymphopenia. Puck JM. Immunol Rev. 2019 Jan;287(1):241-252. doi: 10.1111/imr.12729.

Psychosocial services for primary immunodeficiency disorder families during hematopoietic cell transplantation: A descriptive study. Mangurian C, Scalchunes C, Yoo J, Logan B, Henderson T, Iyengar S, Smith H, Cowan MJ. Palliat Support Care. 2019 Aug;17(4):409-414. doi: 10.1017/S1478951518000603.

Quality of Life of Patients with Wiskott Aldrich Syndrome and X-Linked Thrombocytopenia: a Study of the Primary Immune Deficiency Consortium (PIDTC), Immune Deficiency Foundation, and the Wiskott-Aldrich Foundation. Shah AJ, Sokolic R, Logan B, Yin Z, Iyengar S, Scalchunes C, Mangurian C, Albert M, Cowan MJ. J Clin Immunol. 2019 Nov;39(8):786-794. doi: 10.1007/s10875-019-00689-2. Epub 2019 Oct 16.

Reference intervals for lymphocyte subsets in preterm and term neonates without immune defects. Amatuni GS, Sciortino S, Currier RJ, Naides SJ, Church JA, Puck JM. J Allergy Clin Immunol. 2019 Dec;144(6):1674-1683. doi: 10.1016/j.jaci.2019.05.038. Epub 2019 Jun 18.

Supporting caregivers during hematopoietic cell transplantation for children with primary immunodeficiency disorders. Yoo J, Halley MC, Lown EA, Yank V, Ort K, Cowan MJ, Dorsey MJ, Smith H, Iyengar S, Scalchunes C, Mangurian C. J Allergy Clin Immunol. 2019 Jun;143(6):2271-2278. doi: 10.1016/j.jaci.2018.10.017. Epub 2018 Oct 25.

The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018). Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Logan B, Griffith LM, Kohn DB, Pai SY, Notarangelo L, Shearer W, Prockop S, Kapoor N, Heimall J, Chaudhury S, Shyr D, Chandra S, Cuvelier G, Moore T, Shenoy S, Goldman F, Smith AR, Sunkersett G, Vander Lugt M, Caywood E, Quigg T, Torgerson T, Chandrakasan S, Craddock J, Dávila Saldaña BJ, Gillio A, Shereck E, Aquino V, DeSantes K, Knutsen A, Thakar M, Yu L, Puck JM. J Allergy Clin Immunol. 2019 Jan;143(1):405-407. doi: 10.1016/j.jaci.2018.08.027. Epub 2018 Sep 5.

Advances and highlights in primary immunodeficiencies in 2017. Chinen J, Cowan MJ. J Allergy Clin Immunol. 2018 Oct;142(4):1041-1051. doi: 10.1016/j.jaci.2018.08.016. Epub 2018 Aug 29.

Application of a radiosensitivity flow assay in a patient with DNA ligase 4 deficiency. Buchbinder D, Smith MJ, Kawahara M, Cowan MJ, Buzby JS, Abraham RS. Blood Adv. 2018 Aug 14;2(15):1828-1832. doi: 10.1182/bloodadvances.2018016113.

B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Miggelbrink AM, Logan BR, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Abdel-Azim H, Prockop SE, Shyr D, Decaluwe H, Hanson IC, Gillio A, Dávila Saldaña BJ, Eibel H, Hopkins G, Walter JE, Whangbo JS, Kohn DB, Puck JM, Cowan MJ, Griffith LM, Haddad E, O'Reilly RJ, Notarangelo LD, Pai SY. Blood. 2018 Jun 28;131(26):2967-2977. doi: 10.1182/blood-2017-10-809822. Epub 2018 May 4.

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations. Leiding JW, Okada S, Hagin D, Abinun M, Shcherbina A, Balashov DN, Kim VHD, Ovadia A, Guthery SL, Pulsipher M, Lilic D, Devlin LA, Christie S, Depner M, Fuchs S, van Royen-Kerkhof A, Lindemans C, Petrovic A, Sullivan KE, Bunin N, Kilic SS, Arpaci F, Calle-Martin O, Martinez-Martinez L, Aldave JC, Kobayashi M, Ohkawa T, Imai K, Iguchi A, Roifman CM, Gennery AR, Slatter M, Ochs HD, Morio T, Torgerson TR; Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium. J Allergy Clin Immunol. 2018 Feb;141(2):704-717.e5. doi: 10.1016/j.jaci.2017.03.049. Epub 2017 Jun 7.

Lessons for Sequencing from the Addition of Severe Combined Immunodeficiency to Newborn Screening Panels. Puck JM. Hastings Cent Rep. 2018 Jul;48 Suppl 2(Suppl 2):S7-S9. doi: 10.1002/hast.875.

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study. Barzaghi F, Amaya Hernandez LC, Neven B, Ricci S, Kucuk ZY, Bleesing JJ, Nademi Z, Slatter MA, Ulloa ER, Shcherbina A, Roppelt A, Worth A, Silva J, Aiuti A, Murguia-Favela L, Speckmann C, Carneiro-Sampaio M, Fernandes JF, Baris S, Ozen A, Karakoc-Aydiner E, Kiykim A, Schulz A, Steinmann S, Notarangelo LD, Gambineri E, Lionetti P, Shearer WT, Forbes LR, Martinez C, Moshous D, Blanche S, Fisher A, Ruemmele FM, Tissandier C, Ouachee-Chardin M, Rieux-Laucat F, Cavazzana M, Qasim W, Lucarelli B, Albert MH, Kobayashi I, Alonso L, Diaz De Heredia C, Kanegane H, Lawitschka A, Seo JJ, Gonzalez-Vicent M, Diaz MA, Goyal RK, Sauer MG, Yesilipek A, Kim M, Yilmaz-Demirdag Y, Bhatia M, Khlevner J, Richmond Padilla EJ, Martino S, Montin D, Neth O, Molinos-Quintana A, Valverde-Fernandez J, Broides A, Pinsk V, Ballauf A, Haerynck F, Bordon V, Dhooge C, Garcia-Lloret ML, Bredius RG, Kałwak K, Haddad E, Seidel MG, Duckers G, Pai SY, Dvorak CC, Ehl S, Locatelli F, Goldman F, Gennery AR, Cowan MJ, Roncarolo MG, Bacchetta R; Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT). J Allergy Clin Immunol. 2018 Mar;141(3):1036-1049.e5. doi: 10.1016/j.jaci.2017.10.041. Epub 2017 Dec 11.

Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients. Langelier C, Zinter MS, Kalantar K, Yanik GA, Christenson S, O'Donovan B, White C, Wilson M, Sapru A, Dvorak CC, Miller S, Chiu CY, DeRisi JL. Am J Respir Crit Care Med. 2018 Feb 15;197(4):524-528. doi: 10.1164/rccm.201706-1097LE.

Outcome of domino hematopoietic stem cell transplantation in human subjects: An international case series. Belderbos ME, Gennery AR, Dvorak CC, Blok HJ, Eikema DJ, Silva JMF, Veys P, Neven B, Buckley R, Cole T, Cowan MJ, Goebel WS, Hoenig M, Kuo CY, Stiehm ER, Wynn R, Bierings M; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium. J Allergy Clin Immunol. 2018 Nov;142(5):1628-1631.e4. doi: 10.1016/j.jaci.2018.06.030. Epub 2018 Jul 5.

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. Slack J, Albert MH, Balashov D, Belohradsky BH, Bertaina A, Bleesing J, Booth C, Buechner J, Buckley RH, Ouachée-Chardin M, Deripapa E, Drabko K, Eapen M, Feuchtinger T, Finocchi A, Gaspar HB, Ghosh S, Gillio A, Gonzalez-Granado LI, Grunebaum E, Güngör T, Heilmann C, Helminen M, Higuchi K, Imai K, Kalwak K, Kanazawa N, Karasu G, Kucuk ZY, Laberko A, Lange A, Mahlaoui N, Meisel R, Moshous D, Muramatsu H, Parikh S, Pasic S, Schmid I, Schuetz C, Schulz A, Schultz KR, Shaw PJ, Slatter MA, Sykora KW, Tamura S, Taskinen M, Wawer A, Wolska-Kuśnierz B, Cowan MJ, Fischer A, Gennery AR; Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies; Stem Cell Transplant for Immunodeficiencies in Europe (SCETIDE); Center for International Blood and Marrow Transplant Research; Primary Immunodeficiency Treatment Consortium. J Allergy Clin Immunol. 2018 Jan;141(1):322-328.e10. doi: 10.1016/j.jaci.2017.02.036. Epub 2017 Apr 7.

SCID genotype and 6-month post-transplant CD4 count predict survival and immune recovery: a PIDTC retrospective study. Haddad E, Logan BR, Griffith LM, et al. Blood. Aug 2018. PMID: 30154114. Pending PMCID.

Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome. Kuo CY, Long JD, Campo-Fernandez B, de Oliveira S, Cooper AR, Romero Z, Hoban MD, Joglekar AV, Lill GR, Kaufman ML, Fitz-Gibbon S, Wang X, Hollis RP, Kohn DB. Cell Rep. 2018 May 29;23(9):2606-2616. doi: 10.1016/j.celrep.2018.04.103.

Very early-onset inflammatory bowel disease: an integrated approach. Sullivan KE, Conrad M, Kelsen JR. Curr Opin Allergy Clin Immunol. 2018 Dec;18(6):459-469. doi: 10.1097/ACI.0000000000000484.

Abnormalities of T-cell receptor repertoire in CD4(+) regulatory and conventional T cells in patients with RAG mutations: Implications for autoimmunity. Rowe JH, Stadinski BD, Henderson LA, Ott de Bruin L, Delmonte O, Lee YN, de la Morena MT, Goyal RK, Hayward A, Huang CH, Kanariou M, King A, Kuijpers TW, Soh JY, Neven B, Walter JE, Huseby ES, Notarangelo LD. J Allergy Clin Immunol. 2017 Dec;140(6):1739-1743.e7. doi: 10.1016/j.jaci.2017.08.001. Epub 2017 Aug 31.

Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Heimall J, Puck J, Buckley R, Fleisher TA, Gennery AR, Neven B, Slatter M, Haddad E, Notarangelo LD, Baker KS, Dietz AC, Duncan C, Pulsipher MA, Cowan MJ. Biol Blood Marrow Transplant. 2017 Mar;23(3):379-387. doi: 10.1016/j.bbmt.2016.12.619. Epub 2017 Jan 6.

Estimated disease incidence of RAG1/2 mutations: A case report and querying the Exome Aggregation Consortium. Kumánovics A, Lee YN, Close DW, Coonrod EM, Ujhazi B, Chen K, MacArthur DG, Krivan G, Notarangelo LD, Walter JE. J Allergy Clin Immunol. 2017 Feb;139(2):690-692.e3. doi: 10.1016/j.jaci.2016.07.027. Epub 2016 Sep 5.

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Pulsipher MA, Parikh S, Martinez C, Kapoor N, O'Reilly R, Boyer M, Pai SY, Goldman F, Burroughs L, Chandra S, Kletzel M, Thakar M, Connelly J, Cuvelier G, Davila Saldana BJ, Shereck E, Knutsen A, Sullivan KE, DeSantes K, Gillio A, Haddad E, Petrovic A, Quigg T, Smith AR, Stenger E, Yin Z, Shearer WT, Fleisher T, Buckley RH, Dvorak CC. Blood. 2017 Dec 21;130(25):2718-2727. doi: 10.1182/blood-2017-05-781849. Epub 2017 Oct 11.

Lentivirus Mediated Correction of Artemis-Deficient Severe Combined Immunodeficiency. Punwani D, Kawahara M, Yu J, Sanford U, Roy S, Patel K, Carbonaro DA, Karlen AD, Khan S, Cornetta K, Rothe M, Schambach A, Kohn DB, Malech HL, McIvor RS, Puck JM, Cowan MJ. Hum Gene Ther. 2017 Jan;28(1):112-124. doi: 10.1089/hum.2016.064. Epub 2016 Sep 7.

Long term outcomes of severe combined immunodeficiency: therapy implications. Heimall J, Cowan MJ. Expert Rev Clin Immunol. 2017 Nov;13(11):1029-1040. doi: 10.1080/1744666X.2017.1381558. Epub 2017 Sep 23.

Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, Chandra S, Murguia-Favela L, Bonilla FA, Kanariou M, Damrongwatanasuk R, Kuo CY, Dvorak CC, Meyts I, Chen K, Kobrynski L, Kapoor N, Richter D, DiGiovanni D, Dhalla F, Farmaki E, Speckmann C, Español T, Shcherbina A, Hanson IC, Litzman J, Routes JM, Wong M, Fuleihan R, Seneviratne SL, Small TN, Janda A, Bezrodnik L, Seger R, Raccio AG, Edgar JD, Chou J, Abbott JK, van Montfrans J, González-Granado LI, Bunin N, Kutukculer N, Gray P, Seminario G, Pasic S, Aquino V, Wysocki C, Abolhassani H, Dorsey M, Cunningham-Rundles C, Knutsen AP, Sleasman J, Costa Carvalho BT, Condino-Neto A, Grunebaum E, Chapel H, Ochs HD, Filipovich A, Cowan M, Gennery A, Cant A, Notarangelo LD, Roifman CM. J Allergy Clin Immunol. 2017 Apr;139(4):1282-1292. doi: 10.1016/j.jaci.2016.07.039. Epub 2016 Sep 30.

Neurologic event-free survival demonstrates a benefit for SCID patients diagnosed by newborn screening. Dvorak CC, Puck JM, Wahlstrom JT, Dorsey M, Melton A, Cowan MJ. Blood Adv. 2017 Sep 5;1(20):1694-1698. doi: 10.1182/bloodadvances.2017010835. eCollection 2017 Sep 12.

Newborn screening for severe combined immunodeficiency: a primer for clinicians. Biggs CM, Haddad E, Issekutz TB, Roifman CM, Turvey SE. CMAJ. 2017 Dec 18;189(50):E1551-E1557. doi: 10.1503/cmaj.170561.

Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Heimall J, Buckley RH, Puck J, Fleisher TA, Gennery AR, Haddad E, Neven B, Slatter M, Roderick S, Baker KS, Dietz AC, Duncan C, Griffith LM, Notarangelo L, Pulsipher MA, Cowan MJ. Biol Blood Marrow Transplant. 2017 Aug;23(8):1229-1240. doi: 10.1016/j.bbmt.2017.04.026. Epub 2017 May 4.

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. Hoenig M, Lagresle-Peyrou C, Pannicke U, Notarangelo LD, Porta F, Gennery AR, Slatter M, Cowan MJ, Stepensky P, Al-Mousa H, Al-Zahrani D, Pai SY, Al Herz W, Gaspar HB, Veys P, Oshima K, Imai K, Yabe H, Noroski LM, Wulffraat NM, Sykora KW, Soler-Palacin P, Muramatsu H, Al Hilali M, Moshous D, Debatin KM, Schuetz C, Jacobsen EM, Schulz AS, Schwarz K, Fischer A, Friedrich W, Cavazzana M; European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party. Blood. 2017 May 25;129(21):2928-2938. doi: 10.1182/blood-2016-11-745638. Epub 2017 Mar 22.

The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Defining the Unique Late Effects of Children Undergoing Hematopoietic Cell Transplantation for Immune Deficiencies, Inherited Marrow Failure Disorders, and Hemoglobinopathies. Dietz AC, Duncan CN, Alter BP, Bresters D, Cowan MJ, Notarangelo L, Rosenberg PS, Shenoy S, Skinner R, Walters MC, Wagner J, Baker KS, Pulsipher MA. Biol Blood Marrow Transplant. 2017 Jan;23(1):24-29. doi: 10.1016/j.bbmt.2016.10.004. Epub 2016 Oct 11.

Transplacental maternal engraftment and posttransplantation graft-versus-host disease in children with severe combined immunodeficiency. Wahlstrom J, Patel K, Eckhert E, Kong D, Horn B, Cowan MJ, Dvorak CC. J Allergy Clin Immunol. 2017 Feb;139(2):628-633.e10. doi: 10.1016/j.jaci.2016.04.049. Epub 2016 Jun 16.

Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening. Dorsey MJ, Dvorak CC, Cowan MJ, Puck JM. J Allergy Clin Immunol. 2017 Mar;139(3):733-742. doi: 10.1016/j.jaci.2017.01.005.

Unconditioned unrelated donor bone marrow transplantation for IL7Rα- and Artemis-deficient SCID. Dvorak CC, Patel K, Puck JM, Wahlstrom J, Dorsey MJ, Adams R, Facchino J, Cowan MJ. Bone Marrow Transplant. 2017 Jul;52(7):1036-1038. doi: 10.1038/bmt.2017.74. Epub 2017 Apr 24.

A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70. Chan AY, Punwani D, Kadlecek TA, Cowan MJ, Olson JL, Mathes EF, Sunderam U, Fu SM, Srinivasan R, Kuriyan J, Brenner SE, Weiss A, Puck JM. J Exp Med. 2016 Feb 8;213(2):155-65. doi: 10.1084/jem.20150888. Epub 2016 Jan 18.

Advances in clinical immunology in 2015. Chinen J, Notarangelo LD, Shearer WT. J Allergy Clin Immunol. 2016 Dec;138(6):1531-1540. doi: 10.1016/j.jaci.2016.10.005.

Characterization of T and B cell repertoire diversity in patients with RAG deficiency. Lee YN, Frugoni F, Dobbs K, Tirosh I, Du L, Ververs FA, Ru H, Ott de Bruin L, Adeli M, Bleesing JH, Buchbinder D, Butte MJ, Cancrini C, Chen K, Choo S, Elfeky RA, Finocchi A, Fuleihan RL, Gennery AR, El-Ghoneimy DH, Henderson LA, Al-Herz W, Hossny E, Nelson RP, Pai SY, Patel NC, Reda SM, Soler-Palacin P, Somech R, Palma P, Wu H, Giliani S, Walter JE, Notarangelo LD. Sci Immunol. 2016 Dec 16;1(6):eaah6109. doi: 10.1126/sciimmunol.aah6109. Epub 2016 Dec 16.

Clinically focused exome sequencing identifies an homozygous mutation that confers DOCK8 deficiency. Burbank AJ, Shah SN, Montgomery M, Peden D, Tarrant TK, Weimer ET. Pediatr Allergy Immunol. 2016 Feb;27(1):96-8. doi: 10.1111/pai.12451. Epub 2015 Oct 12.

Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation. Jackson SW, Scharping NE, Jacobs HM, Wang S, Chait A, Rawlings DJ. J Immunol. 2016 Dec 15;197(12):4529-4534. doi: 10.4049/jimmunol.1601198. Epub 2016 Nov 11.

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming. Selleri S, Bifsha P, Civini S, Pacelli C, Dieng MM, Lemieux W, Jin P, Bazin R, Patey N, Marincola FM, Moldovan F, Zaouter C, Trudeau LE, Benabdhalla B, Louis I, Beauséjour C, Stroncek D, Le Deist F, Haddad E. Oncotarget. 2016 May 24;7(21):30193-210. doi: 10.18632/oncotarget.8623.

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. De Ravin SS, Wu X, Moir S, Anaya-O'Brien S, Kwatemaa N, Littel P, Theobald N, Choi U, Su L, Marquesen M, Hilligoss D, Lee J, Buckner CM, Zarember KA, O'Connor G, McVicar D, Kuhns D, Throm RE, Zhou S, Notarangelo LD, Hanson IC, Cowan MJ, Kang E, Hadigan C, Meagher M, Gray JT, Sorrentino BP, Malech HL, Kardava L. Sci Transl Med. 2016 Apr 20;8(335):335ra57. doi: 10.1126/scitranslmed.aad8856.

Lung Disease in Primary Antibody Deficiencies. Schussler E, Beasley MB, Maglione PJ. J Allergy Clin Immunol Pract. 2016 Nov-Dec;4(6):1039-1052. doi: 10.1016/j.jaip.2016.08.005.

Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC. Blood. 2016 Aug 11;128(6):783-93. doi: 10.1182/blood-2015-10-676304. Epub 2016 Jun 14.

Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B. Punwani D, Zhang Y, Yu J, Cowan MJ, Rana S, Kwan A, Adhikari AN, Lizama CO, Mendelsohn BA, Fahl SP, Chellappan A, Srinivasan R, Brenner SE, Wiest DL, Puck JM. N Engl J Med. 2016 Dec 1;375(22):2165-2176. doi: 10.1056/NEJMoa1509164.

Primary Immune Deficiency Treatment Consortium (PIDTC) update. Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E; workshop participants. J Allergy Clin Immunol. 2016 Aug;138(2):375-85. doi: 10.1016/j.jaci.2016.01.051. Epub 2016 Apr 22.

The Primary Immune Deficiency Treatment Consortium: how can it improve definitive therapy for PID?. Cowan MJ. Expert Rev Clin Immunol. 2016 Oct;12(10):1007-9. doi: 10.1080/1744666X.2016.1216317. Epub 2016 Jul 29.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Advances in basic and clinical immunology in 2014. Chinen J, Notarangelo LD, Shearer WT. J Allergy Clin Immunol. May 2015;135(5):1132-1141. PMID: 25956014. Pending PMCID.

Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency. Walter JE, Rosen LB, Csomos K, Rosenberg JM, Mathew D, Keszei M, Ujhazi B, Chen K, Lee YN, Tirosh I, Dobbs K, Al-Herz W, Cowan MJ, Puck J, Bleesing JJ, Grimley MS, Malech H, De Ravin SS, Gennery AR, Abraham RS, Joshi AY, Boyce TG, Butte MJ, Nadeau KC, Balboni I, Sullivan KE, Akhter J, Adeli M, El-Feky RA, El-Ghoneimy DH, Dbaibo G, Wakim R, Azzari C, Palma P, Cancrini C, Capuder K, Condino-Neto A, Costa-Carvalho BT, Oliveira JB, Roifman C, Buchbinder D, Kumanovics A, Franco JL, Niehues T, Schuetz C, Kuijpers T, Yee C, Chou J, Masaad MJ, Geha R, Uzel G, Gelman R, Holland SM, Recher M, Utz PJ, Browne SK, Notarangelo LD. J Clin Invest. 2015 Nov 2;125(11):4135-48. doi: 10.1172/JCI80477. Epub 2015 Oct 12.

Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation. Punwani D, Wang H, Chan AY, Cowan MJ, Mallott J, Sunderam U, Mollenauer M, Srinivasan R, Brenner SE, Mulder A, Claas FH, Weiss A, Puck JM. J Clin Immunol. 2015 Feb;35(2):135-46. doi: 10.1007/s10875-014-0125-1. Epub 2015 Jan 28.

Coronin-1A: immune deficiency in humans and mice. Punwani D, Pelz B, Yu J, Arva NC, Schafernak K, Kondratowicz K, Makhija M, Puck JM. J Clin Immunol. 2015 Feb;35(2):100-7. doi: 10.1007/s10875-015-0130-z. Epub 2015 Feb 10.

HLA-DRB1454 and predictors of new-onset asthma in HIV-infected Thai children. Bunupuradah T, Hansudewechakul R, Kosalaraksa P, et al. Clin Immunol. Mar 2015;157(1):26-29. PMID: 25546395. Pending PMCID.

Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency. Wahlstrom JT, Dvorak CC, Cowan MJ. Curr Pediatr Rep. 2015 Mar 1;3(1):1-10. doi: 10.1007/s40124-014-0071-7.

History and current status of newborn screening for severe combined immunodeficiency. Kwan A, Puck JM. Semin Perinatol. 2015 Apr;39(3):194-205. doi: 10.1053/j.semperi.2015.03.004. Epub 2015 Apr 30.

IL-10/Janus kinase/signal transducer and activator of transcription 3 signaling dysregulates Bim expression in autoimmune lymphoproliferative syndrome. Niss O, Sholl A, Bleesing JJ, Hildeman DA. J Allergy Clin Immunol. 2015 Mar;135(3):762-70. doi: 10.1016/j.jaci.2014.07.020. Epub 2014 Aug 28.

Identification of patients with RAG mutations previously diagnosed with common variable immunodeficiency disorders. Buchbinder D, Baker R, Lee YN, Ravell J, Zhang Y, McElwee J, Nugent D, Coonrod EM, Durtschi JD, Augustine NH, Voelkerding KV, Csomos K, Rosen L, Browne S, Walter JE, Notarangelo LD, Hill HR, Kumánovics A. J Clin Immunol. 2015 Feb;35(2):119-24. doi: 10.1007/s10875-014-0121-5. Epub 2014 Dec 17.

Identification of resolvin D2 receptor mediating resolution of infections and organ protection. Chiang N, Dalli J, Colas RA, Serhan CN. J Exp Med. 2015 Jul 27;212(8):1203-17. doi: 10.1084/jem.20150225. Epub 2015 Jul 20.

Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis. Walter JE, Lo MS, Kis-Toth K, Tirosh I, Frugoni F, Lee YN, Csomos K, Chen K, Pillai S, Dunham J, Tsokos GC, Luning Prak ET, Notarangelo LD. J Allergy Clin Immunol. 2015 Jan;135(1):272-3. doi: 10.1016/j.jaci.2014.07.063. Epub 2014 Oct 11.

Improved outcomes on subcutaneous IgG in patients with humoral immunodeficiency and co-morbid bowel disease. Shah SN, Todoric K, Tarrant TK. Clin Case Rep Rev. 2015 Jul 28;1(7):151-152. doi: 10.15761/CCRR.1000149.

Molecular mechanisms of functional natural killer deficiency in patients with partial DiGeorge syndrome. Zheng P, Noroski LM, Hanson IC, et al. J Allergy Clin Immunol. May 2015;135(5):1293-1302. PMID: 25748067, PMCID: PMC5540306 

New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients. Zinter MS, Dvorak CC, Spicer A, Cowan MJ, Sapru A. Crit Care Med. 2015 Sep;43(9):1986-94. doi: 10.1097/CCM.0000000000001085.

Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use. Long-Boyle JR, Savic R, Yan S, Bartelink I, Musick L, French D, Law J, Horn B, Cowan MJ, Dvorak CC. Ther Drug Monit. 2015 Apr;37(2):236-45. doi: 10.1097/FTD.0000000000000131.

Radiation-sensitive severe combined immunodeficiency: The arguments for and against conditioning before hematopoietic cell transplantation--what to do?. Cowan MJ, Gennery AR. J Allergy Clin Immunol. 2015 Nov;136(5):1178-85. doi: 10.1016/j.jaci.2015.04.027. Epub 2015 Jun 6.

Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. Rissone A, Weinacht KG, la Marca G, Bishop K, Giocaliere E, Jagadeesh J, Felgentreff K, Dobbs K, Al-Herz W, Jones M, Chandrasekharappa S, Kirby M, Wincovitch S, Simon KL, Itan Y, DeVine A, Schlaeger T, Schambach A, Sood R, Notarangelo LD, Candotti F. J Exp Med. 2015 Jul 27;212(8):1185-202. doi: 10.1084/jem.20141286. Epub 2015 Jul 6.

Successful newborn screening for SCID in the Navajo Nation. Kwan A, Hu D, Song M, Gomes H, Brown DR, Bourque T, Gonzalez-Espinosa D, Lin Z, Cowan MJ, Puck JM. Clin Immunol. 2015 May;158(1):29-34. doi: 10.1016/j.clim.2015.02.015. Epub 2015 Mar 8.

A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency. Abolhassani H, Wang N, Aghamohammadi A, Rezaei N, Lee YN, Frugoni F, Notarangelo LD, Pan-Hammarström Q, Hammarström L. J Allergy Clin Immunol. 2014 Dec;134(6):1375-1380. doi: 10.1016/j.jaci.2014.04.042. Epub 2014 Jul 2.

A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency. Lee YN, Frugoni F, Dobbs K, Walter JE, Giliani S, Gennery AR, Al-Herz W, Haddad E, LeDeist F, Bleesing JH, Henderson LA, Pai SY, Nelson RP, El-Ghoneimy DH, El-Feky RA, Reda SM, Hossny E, Soler-Palacin P, Fuleihan RL, Patel NC, Massaad MJ, Geha RS, Puck JM, Palma P, Cancrini C, Chen K, Vihinen M, Alt FW, Notarangelo LD. J Allergy Clin Immunol. 2014 Apr;133(4):1099-108. doi: 10.1016/j.jaci.2013.10.007. Epub 2013 Nov 28.

Advances in basic and clinical immunology in 2013. Chinen J, Notarangelo LD, Shearer WT. J Allergy Clin Immunol. 2014 Apr;133(4):967-76. doi: 10.1016/j.jaci.2014.01.026. Epub 2014 Feb 28.

Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations. Chen K, Wu W, Mathew D, Zhang Y, Browne SK, Rosen LB, McManus MP, Pulsipher MA, Yandell M, Bohnsack JF, Jorde LB, Notarangelo LD, Walter JE. J Allergy Clin Immunol. 2014 Mar;133(3):880-2.e10. doi: 10.1016/j.jaci.2013.11.038. Epub 2014 Jan 25.

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. Dvorak CC, Hassan A, Slatter MA, Hönig M, Lankester AC, Buckley RH, Pulsipher MA, Davis JH, Güngör T, Gabriel M, Bleesing JH, Bunin N, Sedlacek P, Connelly JA, Crawford DF, Notarangelo LD, Pai SY, Hassid J, Veys P, Gennery AR, Cowan MJ. J Allergy Clin Immunol. 2014 Oct;134(4):935-943.e15. doi: 10.1016/j.jaci.2014.06.021. Epub 2014 Aug 7.

Control lymphocyte subsets: can one country's values serve for another's?. Mandala WL, Ananworanich J, Apornpong T, et al. J Allergy Clin Immunol. Sep 2014;134(3):759-761 e758. PMID: 25171870, PMCID: PMC4150016.

Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. J Allergy Clin Immunol. 2014 Apr;133(4):1092-8. doi: 10.1016/j.jaci.2013.09.044. Epub 2013 Nov 28.

Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. Johnson TS, Terrell CE, Millen SH, Katz JD, Hildeman DA, Jordan MB. J Immunol. 2014 Jan 1;192(1):84-91. doi: 10.4049/jimmunol.1302282. Epub 2013 Nov 20.

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, Baker M, Ballow M, Bartoshesky LE, Bonilla FA, Brokopp C, Brooks E, Caggana M, Celestin J, Church JA, Comeau AM, Connelly JA, Cowan MJ, Cunningham-Rundles C, Dasu T, Dave N, De La Morena MT, Duffner U, Fong CT, Forbes L, Freedenberg D, Gelfand EW, Hale JE, Hanson IC, Hay BN, Hu D, Infante A, Johnson D, Kapoor N, Kay DM, Kohn DB, Lee R, Lehman H, Lin Z, Lorey F, Abdel-Mageed A, Manning A, McGhee S, Moore TB, Naides SJ, Notarangelo LD, Orange JS, Pai SY, Porteus M, Rodriguez R, Romberg N, Routes J, Ruehle M, Rubenstein A, Saavedra-Matiz CA, Scott G, Scott PM, Secord E, Seroogy C, Shearer WT, Siegel S, Silvers SK, Stiehm ER, Sugerman RW, Sullivan JL, Tanksley S, Tierce ML 4th, Verbsky J, Vogel B, Walker R, Walkovich K, Walter JE, Wasserman RL, Watson MS, Weinberg GA, Weiner LB, Wood H, Yates AB, Puck JM, Bonagura VR. JAMA. 2014 Aug 20;312(7):729-38. doi: 10.1001/jama.2014.9132.

Primary Immune Deficiency Treatment Consortium (PIDTC) report. Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC; workshop participants. J Allergy Clin Immunol. 2014 Feb;133(2):335-47. doi: 10.1016/j.jaci.2013.07.052. Epub 2013 Oct 15.

Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. Medical Advisory Committee of the Immune Deficiency Foundation, Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM, Bonilla FA, Conley ME, Cunningham-Rundles C, Filipovich AH, Fuleihan R, Gelfand EW, Hernandez-Trujillo V, Holland SM, Hong R, Lederman HM, Malech HL, Miles S, Notarangelo LD, Ochs HD, Orange JS, Puck JM, Routes JM, Stiehm ER, Sullivan K, Torgerson T, Winkelstein J. J Allergy Clin Immunol. 2014 Apr;133(4):961-6. doi: 10.1016/j.jaci.2013.11.043. Epub 2014 Feb 28.

SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID. Schuetz C, Neven B, Dvorak CC, Leroy S, Ege MJ, Pannicke U, Schwarz K, Schulz AS, Hoenig M, Sparber-Sauer M, Gatz SA, Denzer C, Blanche S, Moshous D, Picard C, Horn BN, de Villartay JP, Cavazzana M, Debatin KM, Friedrich W, Fischer A, Cowan MJ. Blood. 2014 Jan 9;123(2):281-9. doi: 10.1182/blood-2013-01-476432. Epub 2013 Oct 21.

Stem cell transplantation for primary immunodeficiency diseases: the North American experience. Pai SY, Cowan MJ. Curr Opin Allergy Clin Immunol. 2014 Dec;14(6):521-6. doi: 10.1097/ACI.0000000000000115.

Survey on retransplantation criteria for patients with severe combined immunodeficiency. Haddad E, Allakhverdi Z, Griffith LM, Cowan MJ, Notarangelo LD. J Allergy Clin Immunol. 2014 Feb;133(2):597-9. doi: 10.1016/j.jaci.2013.10.022. Epub 2013 Dec 10.

Transplantation outcomes for severe combined immunodeficiency, 2000-2009. Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.

Advances in basic and clinical immunology in 2012. Chinen J, Notarangelo LD, Shearer WT. J Allergy Clin Immunol. Mar 2013;131(3):675-682. PMID: 23374612. Pending PMCID.

B-cell reconstitution for SCID: should a conditioning regimen be used in SCID treatment?. Haddad E, Leroy S, Buckley RH. J Allergy Clin Immunol. 2013 Apr;131(4):994-1000. doi: 10.1016/j.jaci.2013.01.047. Epub 2013 Mar 5.

Controversies in IgG replacement therapy in patients with antibody deficiency diseases. Gelfand EW, Ochs HD, Shearer WT. J Allergy Clin Immunol. Apr 2013;131(4):1001-1005. PMID: 23540617. Pending PMCID.

Cord-blood-derived mesenchymal stromal cells downmodulate CD4+ T-cell activation by inducing IL-10-producing Th1 cells. Selleri S, Dieng MM, Nicoletti S, Louis I, Beausejour C, Le Deist F, Haddad E. Stem Cells Dev. 2013 Apr 1;22(7):1063-75. doi: 10.1089/scd.2012.0315. Epub 2013 Jan 4.

Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation. Savic RM, Cowan MJ, Dvorak CC, Pai SY, Pereira L, Bartelink IH, Boelens JJ, Bredius RG, Wynn RF, Cuvelier GD, Shaw PJ, Slatter MA, Long-Boyle J. Biol Blood Marrow Transplant. 2013 Nov;19(11):1608-14. doi: 10.1016/j.bbmt.2013.08.014. Epub 2013 Sep 9.

Expanding the spectrum of recombination-activating gene 1 deficiency: a family with early-onset autoimmunity. Henderson LA, Frugoni F, Hopkins G, de Boer H, Pai SY, Lee YN, Walter JE, Hazen MM, Notarangelo LD. J Allergy Clin Immunol. 2013 Oct;132(4):969-71.e1-2. doi: 10.1016/j.jaci.2013.06.032. Epub 2013 Jul 24.

First reported case of Omenn syndrome in a patient with reticular dysgenesis. Henderson LA, Frugoni F, Hopkins G, Al-Herz W, Weinacht K, Comeau AM, Bonilla FA, Notarangelo LD, Pai SY. J Allergy Clin Immunol. 2013 Apr;131(4):1227-30, 1230.e1-3. doi: 10.1016/j.jaci.2012.07.045. Epub 2012 Sep 24.

Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment. Cattaneo F, Recher M, Masneri S, Baxi SN, Fiorini C, Antonelli F, Wysocki CA, Calderon JG, Eibel H, Smith AR, Bonilla FA, Tsitsikov E, Giliani S, Notarangelo LD, Pai SY. J Allergy Clin Immunol. 2013 Apr;131(4):1136-45. doi: 10.1016/j.jaci.2012.12.667. Epub 2013 Feb 4.

Long-term outcome of non-ablative booster BMT in patients with SCID. Teigland CL, Parrott RE, Buckley RH. Bone Marrow Transplant. 2013 Aug;48(8):1050-5. doi: 10.1038/bmt.2013.6. Epub 2013 Feb 11.

Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. Kwan A, Church JA, Cowan MJ, Agarwal R, Kapoor N, Kohn DB, Lewis DB, McGhee SA, Moore TB, Stiehm ER, Porteus M, Aznar CP, Currier R, Lorey F, Puck JM. J Allergy Clin Immunol. 2013 Jul;132(1):140-50. doi: 10.1016/j.jaci.2013.04.024.

Post-transplantation B cell function in different molecular types of SCID. Buckley RH, Win CM, Moser BK, Parrott RE, Sajaroff E, Sarzotti-Kelsoe M. J Clin Immunol. Jan 2013;33(1):96-110. PMID: 23001410, PMCID: PMC3549311.

The missing vital sign. Mangurian C, Cowan MJ. BMJ. 2013;347:f4163. PMID: 23833077, PMCID: PMC4688548.

The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. Dvorak CC, Cowan MJ, Logan BR, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Shearer WT, O'Reilly RJ, Fleisher TA, Pai SY, Hanson IC, Pulsipher MA, Fuleihan R, Filipovich A, Goldman F, Kapoor N, Small T, Smith A, Chan KW, Cuvelier G, Heimall J, Knutsen A, Loechelt B, Moore T, Buckley RH. J Clin Immunol. 2013 Oct;33(7):1156-64. doi: 10.1007/s10875-013-9917-y. Epub 2013 Jul 2.

Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: need for safer conditioning and reduced late effects. Horn B, Cowan MJ. J Allergy Clin Immunol. 2013 May;131(5):1306-11. doi: 10.1016/j.jaci.2013.03.014.

Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias. Chen R, Giliani S, Lanzi G, Mias GI, Lonardi S, Dobbs K, Manis J, Im H, Gallagher JE, Phanstiel DH, Euskirchen G, Lacroute P, Bettinger K, Moratto D, Weinacht K, Montin D, Gallo E, Mangili G, Porta F, Notarangelo LD, Pedretti S, Al-Herz W, Alfahdli W, Comeau AM, Traister RS, Pai SY, Carella G, Facchetti F, Nadeau KC, Snyder M, Notarangelo LD. J Allergy Clin Immunol. 2013 Sep;132(3):656-664.e17. doi: 10.1016/j.jaci.2013.06.013. Epub 2013 Jul 4.

Advances in basic and clinical immunology in 2011. Chinen J, Shearer WT. J Allergy Clin Immunol. Feb 2012;129(2):342-348. PMID: 22206779, PMCID: PMC3279946.

CD45-deficient severe combined immunodeficiency caused by uniparental disomy. Roberts JL, Buckley RH, Luo B, et al. Proc Natl Acad Sci USA. Jun 26 2012;109(26):10456-10461. PMID: 22689986, PMCID: PMC3387083.

Cellular calibrators to quantitate T-cell receptor excision circles (TRECs) in clinical samples. Punwani D, Gonzalez-Espinosa D, Comeau AM, Dutra A, Pak E, Puck J. Mol Genet Metab. 2012 Nov;107(3):586-91. doi: 10.1016/j.ymgme.2012.09.018. Epub 2012 Sep 21.

Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. Martinez CA, Shah S, Shearer WT, et al. J Allergy Clin Immunol. Jan 2012;129(1):176-183. PMID: 22078471. Pending PMCID.

FTY720 markedly increases alloengraftment but does not eliminate host anti-donor T cells that cause graft rejection on its withdrawal. Taylor PA, Kelly RM, Bade ND, Smith MJ, Stefanski HE, Blazar BR. Biol Blood Marrow Transplant. Sep 2012;18(9):1341-1352. PMID: 22728248, PMCID: PMC3520609.

HCT survival in ADA-SCID: what's the buzz?. Chan SK, Shearer WT. Blood. Oct 25 2012;120 (17):3392-3393. PMID: 23100302. Pending PMCID.

Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents. Siberry GK, Leister E, Jacobson DL, et al. Clin Immunol. Feb 2012;142(2):201-208. PMID: 22094294, PMCID: PMC3273595.

Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles. Puck JM. J Allergy Clin Immunol. 2012 Mar;129(3):607-16. doi: 10.1016/j.jaci.2012.01.032. Epub 2012 Jan 29.

Lymphoma complicating primary immunodeficiency syndromes. Leechawengwongs E, Shearer WT. Curr Opin Hematol. Jul 2012;19(4):305-312. PMID: 22525579. Pending PMCID.

Ruling out HIV infection when testing for severe combined immunodeficiency and other T-cell deficiencies. Hanson IC, Shearer WT. J Allergy Clin Immunol. Mar 2012;129(3):875-876 e875. PMID: 22386446. Pending PMCID.

The long quest for neonatal screening for severe combined immunodeficiency. Buckley RH. J Allergy Clin Immunol. Mar 2012;129(3):597-604; quiz 605-596. PMID: 22277203, PMCID: PMC3294102.

Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. Tison BE, Nicholas SK, Abramson SL, et al. J Allergy Clin Immunol. Nov 2011;128(5):1115-1117 e1111-1113. PMID: 21835443. Pending PMCID.

Chronic granulomatous disease: lessons from a rare disorder. Segal BH, Veys P, Malech H, Cowan MJ. Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S123-31. doi: 10.1016/j.bbmt.2010.09.008.

Decline of antibodies in XLA infant: when to start IVIG. Okocha IU, Hanson CG, Chinen J, Shearer WT. Allergy. 2011 Mar;66(3):434-5. doi: 10.1111/j.1398-9995.2010.02481.x. Epub 2010 Sep 7.

Early versus delayed diagnosis of SCID: triumph versus tragedy. Nicholas S, Krance RA, Hanson IC, et al. Clin Immunol. Jun 2011;139(3):360-362. PMID: 21497138. Pending PMCID.

Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID. Yu GP, Nadeau KC, Berk DR, de Saint Basile G, Lambert N, Knapnougel P, Roberts J, Kavanau K, Dunn E, Stiehm ER, Lewis DB, Umetsu DT, Puck JM, Cowan MJ. Pediatr Transplant. 2011 Nov;15(7):733-41. doi: 10.1111/j.1399-3046.2011.01563.x. Epub 2011 Aug 23.

Hematopoietic stem cell transplantation for CD3δ deficiency. Marcus N, Takada H, Law J, Cowan MJ, Gil J, Regueiro JR, Plaza Lopez de Sabando D, Lopez-Granados E, Dalal J, Friedrich W, Manfred H, Hanson IC, Grunebaum E, Shearer WT, Roifman CM. J Allergy Clin Immunol. 2011 Nov;128(5):1050-7. doi: 10.1016/j.jaci.2011.05.031. Epub 2011 Jul 16.

IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo. Recher M, Berglund LJ, Avery DT, Cowan MJ, Gennery AR, Smart J, Peake J, Wong M, Pai SY, Baxi S, Walter JE, Palendira U, Tangye GA, Rice M, Brothers S, Al-Herz W, Oettgen H, Eibel H, Puck JM, Cattaneo F, Ziegler JB, Giliani S, Tangye SG, Notarangelo LD. Blood. 2011 Dec 22;118(26):6824-35. doi: 10.1182/blood-2011-06-362533. Epub 2011 Oct 28.

Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative study. Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, Cant AJ, Thrasher AJ, Cowan MJ, Albert MH, Small T, Pai SY, Haddad E, Lisa A, Hambleton S, Slatter M, Cavazzana-Calvo M, Mahlaoui N, Picard C, Torgerson TR, Burroughs L, Koliski A, Neto JZ, Porta F, Qasim W, Veys P, Kavanau K, Hönig M, Schulz A, Friedrich W, Notarangelo LD. Blood. 2011 Aug 11;118(6):1675-84. doi: 10.1182/blood-2010-11-319376. Epub 2011 Jun 9.

Neonatal screening for severe combined immunodeficiency. Puck JM. Curr Opin Pediatr. 2011 Dec;23(6):667-73. doi: 10.1097/MOP.0b013e32834cb9b0.

The case for newborn screening for severe combined immunodeficiency and related disorders. Puck JM. Ann N Y Acad Sci. 2011 Dec;1246:108-17. doi: 10.1111/j.1749-6632.2011.06346.x.

Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Buckley RH. Immunol Res. Apr 2011;49(1-3):25-43. PMID: 21116871, PMCID: PMC3798033.

WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity. Becker-Herman S, Meyer-Bahlburg A, Schwartz MA, Jackson SW, Hudkins KL, Liu C, Sather BD, Khim S, Liggitt D, Song W, Silverman GJ, Alpers CE, Rawlings DJ. J Exp Med. Sep 26 2011;208(10):2033-2042. PMID: 21875954, PMCID: PMC3182055.

Advances in basic and clinical immunology in 2009. Chinen J, Shearer WT. J Allergy Clin Immunol. Mar 2010;125(3):563-568. PMID: 20226292, PMCID: PMC2841291.

B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review. Buckley RH. J Allergy Clin Immunol. Apr 2010;125(4):790-797. PMID: 20371393, PMCID: PMC2857969.

Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency. Walter JE, Rucci F, Patrizi L, Recher M, Regenass S, Paganini T, Keszei M, Pessach I, Lang PA, Poliani PL, Giliani S, Al-Herz W, Cowan MJ, Puck JM, Bleesing J, Niehues T, Schuetz C, Malech H, DeRavin SS, Facchetti F, Gennery AR, Andersson E, Kamani NR, Sekiguchi J, Alenezi HM, Chinen J, Dbaibo G, ElGhazali G, Fontana A, Pasic S, Detre C, Terhorst C, Alt FW, Notarangelo LD. J Exp Med. 2010 Jul 5;207(7):1541-54. doi: 10.1084/jem.20091927. Epub 2010 Jun 14.

Radiosensitive severe combined immunodeficiency disease. Dvorak CC, Cowan MJ. Immunol Allergy Clin North Am. 2010 Feb;30(1):125-42. doi: 10.1016/j.iac.2009.10.004.

Secondary immunodeficiencies, including HIV infection. Chinen J, Shearer WT. J Allergy Clin Immunol. 2010 Feb; 125(2 Suppl 2):S195-203. PMID: 20042227. Pending PMCID.

Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Zemble R, Luning Prak E, McDonald K, McDonald-McGinn D, Zackai E, Sullivan K. Clin Immunol. 2010 Sep;136(3):409-18. doi: 10.1016/j.clim.2010.04.011. Epub 2010 May 15.

Advances in basic and clinical immunology in 2008. Chinen J, Shearer WT. J Allergy Clin Immunol. Feb 2009;123(2):328-332. PMID: 19203657. Pending PMCID.

Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT; Workshop Participants. J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12. doi: 10.1016/j.jaci.2009.10.022.

Outcomes of patients with severe combined immunodeficiency treated with hematopoietic stem cell transplantation with and without preconditioning. Patel NC, Chinen J, Rosenblatt HM, et al. J Allergy Clin Immunol. Nov 2009;124(5):1062-1069 e1061-1064. PMID: 19895994, PMCID: PMC3271026.

Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras. Sarzotti-Kelsoe M, Win CM, Parrott RE, et al. Blood. Aug 13 2009;114(7):1445-1453. PMID: 19433858, PMCID: PMC2727406.

Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. Griffith LM, Cowan MJ, Kohn DB, Notarangelo LD, Puck JM, Schultz KR, Buckley RH, Eapen M, Kamani NR, O'Reilly RJ, Parkman R, Roifman CM, Sullivan KE, Filipovich AH, Fleisher TA, Shearer WT. J Allergy Clin Immunol. 2008 Dec;122(6):1087-96. doi: 10.1016/j.jaci.2008.09.045. Epub 2008 Nov 6.

Long-term outcomes of nonconditioned patients with severe combined immunodeficiency transplanted with HLA-identical or haploidentical bone marrow depleted of T cells with anti-CD6 mAb. Patel NC, Chinen J, Rosenblatt HM, et al. J Allergy Clin Immunol. Dec 2008;122(6):1185-1193. PMID: 19084111. Pending PMCID.

Treatment of immunodeficiency: long-term outcome and quality of life. Shearer WT, Notarangelo LD, Griffith LM. J Allergy Clin Immunol. Dec 2008;122(6):1065-1068. PMID: 19084107. Pending PMCID.

Impact of supplementation with L-citrulline/arginine after liver transplantation in individuals with Urea Cycle Disorders. Posset R, Garbade SF, Gleich F, Nagamani SCS, Gropman AL, Epp F, Ramdhouni N, Druck AC, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) consortia study group. Mol Genet Metab. 2024 Mar;141(3):108112. doi: 10.1016/j.ymgme.2023.108112. Epub 2023 Dec 10. PMID: 38301530.

Urea cycle disorders (UCDs) are genetic disorders that result in a deficiency of one of the six enzymes in the urea cycle, causing hyperammonemia (high blood ammonia levels). When medical management is not enough to prevent hyperammonemia, patients with UCDs may undergo liver transplantation. Both before and after transplant, these patients often receive L-citrulline or L-arginine supplements to help their bodies eliminate ammonia. However, not much is known about the impact of long-term supplementation.

In this pilot study, researchers investigated the effects of long-term L-citrulline or L-arginine supplementation in patients with UCDs who have undergone liver transplantation. The team used data collected from longitudinal observational studies to compare outcomes of 16 patients who received these supplements long-term with 36 patients who were not supplemented over the course of 4 or 5 years after transplant.

Results suggest that although supplementation with L-citrulline or L-arginine is often continued after transplant, in this pilot study, such supplementation was not associated with health-related outcomes or biochemical responses. Authors note that analyzing larger samples over longer observation periods will provide more insight into the usefulness of long-term supplementation.

Barriers to a successful healthcare transition for individuals with urea cycle disorders. Ladha FA, Le Mons C, Craigen WJ, Magoulas PL, Marom R, Lewis AM. Mol Genet Metab. 2023 Jul;139(3):107609. doi: 10.1016/j.ymgme.2023.107609. Epub 2023 May 15.

Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance. Stroup BM, Li X, Ho S, Zhouyao H, Chen Y, Ani S, Dawson B, Jin Z, Marom R, Jiang MM, Lorenzo I, Rosen D, Lanza D, Aceves N, Koh S, Seavitt JR, Heaney JD, Lee B, Burrage LC. Dis Model Mech. 2023 Aug 1;16(8):dmm050118. doi: 10.1242/dmm.050118. Epub 2023 Aug 17.

Health-related quality of life in a systematically assessed cohort of children and adults with urea cycle disorders. Murali CN, Barber JR, McCarter R, Zhang A, Gallant N, Simpson K, Dorrani N, Wilkening GN, Hays RD, Lichter-Konecki U; Members of the Urea Cycle Disorders Consortium; Burrage LC, Nagamani SCS. Mol Genet Metab. 2023 Sep 8;140(3):107696. doi: 10.1016/j.ymgme.2023.107696. Epub ahead of print. PMID: 37690181

Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Accumulation of ammonia is toxic to the nervous system, resulting in neurological symptoms that can impact health-related quality of life (HRQoL). However, only a few studies have systematically investigated the impact of UCDs on HRQoL.

In this study, researchers assessed HRQoL in a large cohort of children and adults with UCDs. The team reviewed HRQoL and clinical data from a Urea Cycle Disorders Consortium longitudinal study; compared to healthy individuals and those with PKU and diabetes; and assessed relationships between HRQoL, UCD diagnosis, and disease severity.

Results show that individuals with UCDs have worse HRQoL compared to healthy individuals and those with PKU and diabetes. Authors state that future work should focus on the impact of liver transplantation and other clinical variables on HRQoL in UCDs.

Monitoring the treatment of urea cycle disorders using phenylbutyrate metabolite analyses: Still many lessons to learn. Glinton KE, Minard CG, Liu N, Sun Q, Elsea SH, Burrage LC, Nagamani SCS. Mol Genet Metab. 2023 Nov;140(3):107699. doi: 10.1016/j.ymgme.2023.107699. Epub 2023 Sep 11.

Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders. Posset R, Garbade SF, Gleich F, Scharre S, Okun JG, Gropman AL, Nagamani SCS, Druck AC, Epp F, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC); European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Genet Med. 2023 Dec 3;26(4):101039. doi: 10.1016/j.gim.2023.101039. Epub ahead of print. PMID: 38054409.

Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Patients with UCD may undergo liver transplantation when medical management is not enough to prevent hyperammonemia. However, not much is known about how the effects of transplant compare to medical management alone.

In this study, researchers classified patients into “severe” and “attenuated” categories based on genetic information and a novel enzyme activity test. Then, using data collected from longitudinal observational studies, they compared the health-related outcomes in patients who underwent liver transplantation vs medical management. 

Results show that liver transplantation led to greater metabolic stability without the need for protein restriction or nitrogen-scavenging therapy. However, while transplantation led to more favorable growth outcomes, it was not associated with improved neurocognitive outcomes compared to long-term medical management.

The challenge of understanding and predicting phenotypic diversity in urea cycle disorders. Posset R, Zielonka M, Gleich F, Garbade SF, Hoffmann GF, Kölker S; Urea Cycle Disorders Consortium (UCDC) and European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. J Inherit Metab Dis. 2023 Nov;46(6):1007-1016. doi: 10.1002/jimd.12678. Epub 2023 Oct 10.

Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency. Scharre S, Posset R, Garbade SF, Gleich F, Seidl MJ, Druck AC, Okun JG, Gropman AL, Nagamani SCS, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Ann Clin Transl Neurol. 2022 Oct 10. doi: 10.1002/acn3.51668. Epub ahead of print. PMID: 36217298.

Ornithine transcarbamylase deficiency (OTC-D) is an X-linked disorder and the most common type of urea cycle disorder. Patients with OTC-D can present with a variable spectrum of disease severity, ranging from no symptoms to lethal hyperammonemia (high blood ammonia levels). Therefore, predicting disease course at an early stage is important to personalize therapies for individual patients, which can include medical treatment or liver transplantation. In this study, researchers developed a new cell-based system to assess the residual enzyme activity associated with various disease-causing genetic changes in the OTC gene. Using this system, they were able to correlate residual enzymatic OTC activities with clinical and biochemical outcome parameters of 119 male individuals with OTC-D. Results show that residual enzymatic OTC activity can distinguish individuals with a severe form of OTC-D from those with milder forms of the disorder. As a reliable predictor of disease severity in OTC-D, this classification system could help guide therapeutic strategies and counseling of patients and parents.

Review of Applications of Near-Infrared Spectroscopy in Two Rare Disorders with Executive and Neurological Dysfunction: UCD and PKU. Khaksari K, Chen WL, Gropman AL. Genes (Basel). 2022 Sep 21;13(10):1690. doi: 10.3390/genes13101690. PMID: 36292574; PMCID: PMC9602148.

Urea cycle disorders (UCD) and phenylketonuria (PKU) are two types of genetic, metabolic disorders characterized by neurological symptoms. As with many rare diseases, small population size can make these disorders challenging to study. Tools such as functional neuroimaging are developed to help generate biomarkers, collect baseline data, and measure treatment effects in patients with neurological disorders. However, the cost and infrastructure requirements of these tools have limited their availability. To address this challenge, researchers and clinicians are developing new tools that are non-invasive, portable, and inexpensive. In this review article, researchers discuss the use of functional near-infrared spectroscopy (fNIRS)—a non-invasive, portable tool that uses blood oxygenation to view the brain—in patients with UCD and PKU. Authors consider the ability of fNIRS to obtain biomarkers for screening and monitoring these diseases.

ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype. Lerner S, Eilam R, Adler L, Baruteau J, Kreiser T, Tsoory M, Brandis A, Mehlman T, Ryten M, Botia JA, Ruiz SG, Garcia AC, Dionisi-Vici C, Ranucci G, Spada M, Mazkereth R, McCarter R, Izem R, Balmat TJ, Richesson R; Members of the UCDC, Gazit E, Nagamani SCS, Erez A. Hum Genet. 2021 Oct;140(10):1471-1485. doi: 10.1007/s00439-021-02345-5. Epub 2021 Aug 21.

In the liver, the enzymes argininosuccinate lyase (ASL) and argininosuccinate synthase 1 (ASS1) are required to convert waste-nitrogen to urea. Loss of activity for either enzyme causes argininosuccinate lyase deficiency and citrullinemia type 1, respectively. These two disorders are a subset of the classical inborn errors of metabolism called urea cycle disorders (UCD), characterized by episodes of hyperammonemia. ASL deficiency can also result in impaired nitric oxide (NO) synthesis, decreased tyrosine hydroxylase (TH) activity, and low dopamine and norepinephrine levels in the neuronal cells. Both dopamine and norepinephrine are important neurotransmitters, and their deficiency has been associated with neurodegenerative disorders, including Parkinson's Disease. In this study, researchers used a mouse model with loss of ASL in catecholamine neurons to test the hypothesis that decreased activity of ASL and TH would contribute to neurodegeneration. They found that neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. Study authors say their data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. They suggest that regulating NO levels may be beneficial for the treatment of catecholamine-related neurodegenerative disorders.

Biomarkers for liver disease in urea cycle disorders. Nagamani SCS, Ali S, Izem R, Schady D, Masand P, Shneider BL, Leung DH, Burrage LC. Mol Genet Metab. 2021 Apr 8:S1096-7192(21)00685-5. doi: 10.1016/j.ymgme.2021.04.001. Online ahead of print.

Clinical utility of brain MRS imaging of patients with adult-onset non-cirrhotic hyperammonemia. Stergachis AB, Krier JB, Merugumala SK, Berry GT, Lin AP. Mol Genet Metab Rep. 2021 Mar 13;27:100742. doi: 10.1016/j.ymgmr.2021.100742. eCollection 2021 Jun.

Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism. Liu N, Xiao J, Gijavanekar C, Pappan KL, Glinton KE, Shayota BJ, Kennedy AD, Sun Q, Sutton VR, Elsea SH. JAMA Netw Open. 2021 Jul 1;4(7):e2114155. doi: 10.1001/jamanetworkopen.2021.14155.

Inborn errors of metabolism (IEMs) are rare genetic disorders in which the body cannot properly turn food into energy. Newborn screening (NBS) has improved diagnosis of these diseases, but gaps remain as many of these rare diseases are not included on NBS panels. In this study, researchers evaluated the usefulness of untargeted metabolomics as a primary screening tool, comparing the diagnostic rate of clinical metabolomics to traditional newborn screening. They found that untargeted metabolomics improved the diagnostic rate for IEMs six-fold when compared to the traditional NBS approach. The metabolomics approach also identified a broader spectrum of IEMs. Authors say these data support the use of clinical untargeted metabolomics in screening for IEMs and suggest that broader screening approaches should be considered to help diagnose these rare diseases.

Expanding Role of Proton Magnetic Resonance Spectroscopy: Timely Diagnosis and Treatment Initiation in Partial Ornithine Transcarbamylase Deficiency. Sen K, Castillo Pinto C, Gropman AL. J Pediatr Genet. 2021 Mar;10(1):77-80. doi: 10.1055/s-0040-1709670. Epub 2020 Apr 23.

Fifteen years of urea cycle disorders brain research: Looking back, looking forward. Sen K, Whitehead M, Castillo Pinto C, Caldovic L, Gropman A. Anal Biochem. 2022 Jan 1;636:114343. doi: 10.1016/j.ab.2021.114343. Epub 2021 Oct 9. PMID: 34637785; PMCID: PMC8671367.

This new review paper highlights the evolving knowledge about the impact of urea cycle disorders (UCD) and hyperammonemia (HA) in particular on neurological injury and recovery. It discusses the use of electroencephalography (EEG) and magnetic resonance imaging (MRI) to study and evaluate prognostic factors for risk and recovery. It recognizes the work of others and discusses the UCDC's prior work and future research priorities, as well as lessons learned over 15 years of neuroimaging research. Key learnings include the identification of the insular cortex as the area most vulnerable to hyperammonemia in UCD. Elevated glutamine and decreased myoinosital have been identified as key brain biomarkers on proton magnetic resonance spectroscopy (MRS), with decreased choline seen over time in patients with repeat HA episodes. Slow recovery of brain glutamine after recovery from hyperammonemia is common. Researchers have found that 1H-MRS, a non-invasive technique that enables the detection, identification, and quantification of biochemical compounds or metabolites in the brain tissue, is most sensitive for proximal UCD and is often abnormal with elevated glutamine, before routine T1 and T2 sequences on MRI show abnormalities. In addition, our work demonstrates that more than one-third of female carriers of OTCD have the biochemical phenotype of UCD on MRS including mildly elevated glutamine and lower than normal myoinositol. 1H-MRS should be added to the clinical routine in patients with known and suspected metabolic conditions.

Randomized and non-randomized designs for causal inference with longitudinal data in rare disorders. Izem R, McCarter R. Orphanet J Rare Dis. 2021 Nov 23;16(1):491. doi: 10.1186/s13023-021-02124-5. PMID: 34814939; PMCID: PMC8609847.

Sound study design and causal inference methods are essential to demonstrate the therapeutic efficacy, safety, and effectiveness of new therapies. In the rare diseases setting, the small patient population size, genotypic and phenotypic diversity, and the complexity and incomplete understanding of the disorder's progression challenge the use of typical parallel control designs. This paper reviews longitudinal designs and draws the parallel between some new and existing randomized studies in rare diseases and their less well-known controlled observational study designs. Authors provide examples of analyses in multiple rare disorders, including urea cycle disorder and cystic fibrosis.

Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue. Sen K, Anderson AA, Whitehead MT, Gropman AL. Front Neurol. 2021 Apr 28;12:632307. doi: 10.3389/fneur.2021.632307. eCollection 2021.

The Application of Neurodiagnostic Studies to Inform the Acute Management of a Newborn Presenting With Sarbamoyl Shosphate Synthetase 1 Deficiency. McGowan M, Ferreira C, Whitehead M, Basu SK, Chang T, Gropman A. Child Neurol Open. 2021 Jan 22;8:2329048X20985179. doi: 10.1177/2329048X20985179. eCollection 2021 Jan-Dec.

A novel frameshift mutation in SOX10 causes Waardenburg syndrome with peripheral demyelinating neuropathy, visual impairment and the absence of Hirschsprung disease. Burke EA, Reichard KE, Wolfe LA, Brooks BP, DiGiovanna JJ, Hadley DW, Lehky TJ, Gropman AL, Tifft CJ, Gahl WA, Toro C, Adams D. Am J Med Genet A. 2020 May;182(5):1278-1283. doi: 10.1002/ajmg.a.61542. Epub 2020 Mar 9. PMID: 32150337, PMCID: PMC7167353.

Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency. Burrage LC, Madan S, Li X, Ali S, Mohammad M, Stroup BM, Jiang MM, Cela R, Bertin T, Jin Z, Dai J, Guffey D, Finegold M; Members of the Urea Cycle Disorders Consortium (UCDC), Nagamani S, Minard CG, Marini J, Masand P, Schady D, Shneider BL, Leung DH, Bali D, Lee B. JCI Insight. 2020 Feb 27;5(4):e132342. doi: 10.1172/jci.insight.132342.

In this study, researchers reviewed participant data from the Urea Cycle Disorders Consortium’s (UCDC) Longitudinal Study that included all types of UCD. The data suggested that individuals with argininosuccinate lyase deficiency (ASLD) and arginase deficiency had a higher prevalence of liver injury as compared to other types of UCD. Researchers assessed liver disease in individuals with ASLD and a laboratory mouse model of ASLD. Around 37% individuals with ASLD had increased ALT levels. Some of the ASLD participants were noted to have increased liver stiffness but normal ALT and AST levels. The results showed that a quarter of the participants with normal ALT levels had abnormal liver imaging or testing. The ASLD study mice also developed chronic liver damage. These mice had excessive hepatic glycogen, liver enlargement, and increased ALT and AST levels. Hepatic glycogen accumulation has also been found in other types of UCD. More research is needed to identify the role of hepatic glycogen in UCD, as it is unknown whether it leads to, is the cause of, or is at all connected to damage in the liver. This study shows the need to identify additional biomarkers of liver damage in UCD.

Developing interactions with industry in rare diseases: lessons learned and continuing challenges. Berry SA, Coughlin CR 2nd, McCandless S, McCarter R, Seminara J, Yudkoff M, LeMons C. Genet Med. 2020 Jan;22(1):219-226. doi: 10.1038/s41436-019-0616-9. Epub 2019 Jul 24.

The NIH established the Rare Diseases Clinical Research Network to address the unique challenges of performing research on rare diseases. The UCDC was one of the original ten consortia established. Based in part on financial incentives associated with the Orphan Drug Act of 1983 (a United States law that helped catalyze the development of drugs for rare diseases), biopharmaceutical and investment entities have an intense interest in engaging with rare disease research consortia like the UCDC, which have compiled potentially valuable longitudinal data characterizing outcomes in a relatively large number of affected individuals. Natural history data from the longitudinal study are invaluable not only for the many exploratory studies conducted by the UCDC, but also to industry partners seeking to develop new therapeutics to improve the lives of UCD patients and ultimately a cure. This publication discusses the ways in which the UCDC navigates industry relationships in the pursuit of developing therapeutics for UCD patients. For example, the UCDC has developed a method for evaluating partnerships with private entities, established an Industry Relations Committee in 2015 to develop guiding principles, a policy and procedures for interacting with industry (including protection of data privacy), and managing investigator conflict of interest. By building a framework for industry partnerships that guides us in resolving inevitable challenges, the UCDC can pursue novel and promising collaborations that can lead to breakthroughs in treatment for patients.

Evaluation of neurocognitive function of prefrontal cortex in ornithine transcarbamylase deficiency. Anderson A, Gropman A, Le Mons C, Stratakis C, Gandjbakhche A. Mol Genet Metab. 2020 Mar;129(3):207-212. doi: 10.1016/j.ymgme.2019.12.014. Epub 2020 Jan 10. PMID: 31952925. Full Text.

From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria. Zielonka M, Garbade SF, Gleich F, Okun JG, Nagamani SCS, Gropman AL, Hoffmann GF, Kölker S, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Hum Mutat. 2020 May;41(5):946-960. doi: 10.1002/humu.23983. Epub 2020 Jan 30.

Argininosuccinic aciduria (ASA), caused by a deficiency in argininosuccinate lyase (ASL), is one of the more common urea cycle disorder subtypes. ASA has a wide range of symptoms ranging from mild disease to individuals with significant neurocognitive deficiencies. In this study, researchers analyzed previously collected patient data and correlated these with a new method of enzymatic testing for ASL to determine if the activity level of ASL was a reliable predictor of disease severity. The data was collected from the Longitudinal Study of UCD conducted by the Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD). The results showed that individuals with ASA with 8% or less ASL activity had higher initial ammonia levels and more frequent hyperammonemic episodes per year, and those with 8.7% or less ASL activity had increased liver damage. Overall, older ASL patients performed worse than younger ASL patients, which points to the possibility of chronic cognitive deterioration. The difference was more pronounced for those with ASL activity below 24.3%, suggesting additional underlying factors that affect cognition below a certain level of ASL activity. Based on the outcomes of this and previous studies, there is a possibility that ASL activity levels could help caregivers predict disease severity in ASA patients and inform the development of more effective, individualized treatments.

Hemodynamics of Prefrontal Cortex in Ornithine Transcarbamylase Deficiency: A Twin Case Study. Anderson AA, Gropman A, Le Mons C, Stratakis CA, Gandjbakhche AH. Front Neurol. 2020 Aug 14;11:809. doi: 10.3389/fneur.2020.00809. PMID: 32922350; PMCID: PMC7456944.

Late Onset Ornithine Transcarbamylase Deficiency Triggered by an Acute Increase in Protein Intake: A Review of 10 Cases Reported in the Literature. Barkovich E, Gropman AL. Case Rep Genet. 2020 Apr 25;2020:7024735. doi: 10.1155/2020/7024735. PMID: 32373372; PMCID: PMC7197010. 

Long-term effects of medical management on growth and weight in individuals with urea cycle disorders. Posset R, Garbade SF, Gleich F, Gropman AL, de Lonlay P, Hoffmann GF, Garcia-Cazorla A, Nagamani SCS, Baumgartner MR, Schulze A, Dobbelaere D, Yudkoff M, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC); European registry and network for Intoxication type Metabolic Diseases (E-IMD). Sci Rep. 2020 Jul 20;10(1):11948. doi: 10.1038/s41598-020-67496-3.

Multimodal imaging in urea cycle-related neurological disease - What can imaging after hyperammonemia teach us. Sen K, Whitehead MT, Gropman AL. Transl Sci Rare Dis. 2020 Aug 3;5(1-2):87-95. doi: 10.3233/TRD-200048.

Novel imaging technologies for genetic diagnoses in the inborn errors of metabolism. Gropman AL, Anderson A. J Transl Genet Genom. 2020;4:429-445. doi: 10.20517/jtgg.2020.09. Epub 2020 Nov 13.

Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations. Rech ME, McCarthy JM, Chen CA, Edmond JC, Shah VS, Bosch DGM, Berry GT, Williams L, Madan-Khetarpal S, Niyazov D, Shaw-Smith C, Kovar EM, Lupo PJ, Schaaf CP. Am J Med Genet A. 2020 Apr 10. doi: 10.1002/ajmg.a.61580. PMID: 32275123.

Severity-adjusted evaluation of newborn screening on the metabolic disease course in individuals with cytosolic urea cycle disorders. Posset R, Kölker S, Gleich F, Okun JG, Gropman AL, Nagamani SCS, Scharre S, Probst J, Walter ME, Hoffmann GF, Garbade SF, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) consortia study group. Mol Genet Metab. 2020 Dec;131(4):390-397. doi: 10.1016/j.ymgme.2020.10.013. Epub 2020 Nov 7.

ASL Metabolically Regulates Tyrosine Hydroxylase in the Nucleus Locus Coeruleus. Lerner S, Anderzhanova E, Verbitsky S, Eilam R, Kuperman Y, Tsoory M, Kuznetsov Y, Brandis A, Mehlman T, Mazkereth R; UCDC Neuropsychologists, McCarter R, Segal M, Nagamani SCS, Chen A, Erez A. Cell Rep. 2019 Nov 19;29(8):2144-2153.e7. doi: 10.1016/j.celrep.2019.10.043.

The researchers developed a laboratory mouse model with ASL deficiency in specific regions of the brain and showed that argininosuccinate lyase (ASL) is required for the normal function of the nucleus locus coeruleus (LC) in the brain. LC is the main source of norepinephrine in the brain (an important chemical messenger in the brain and a stress hormone). Loss of ASL in the LC results in low amounts of nitric oxide (NO) which leads to the reduced amount and activity of tyrosine hydroxylase (TH), an enzyme needed to produce dopamine and norepinephrine. The mice with ASL deficiency in LC showed decreased amounts of dopamine and norepinephrine in the brain, displayed higher blood pressure, increased motor activity, and increased sensitivity to develop seizures. Treatment of these mice with donor NO resulted in lower blood pressure and less seizure activity. Behavioral data previously collected from the Longitudinal Study of UCDs (Urea Cycle Disorders) conducted by the Urea Cycle Disorders Consortium showed 55% of participants with ASLD displayed lower attention spans during study visits, compared to 39.4% of participants with another UCD—argininosuccinate synthase deficiency (ASS1D/Citrullinemia). The results were similar for participants who did not have any documented episodes of hyperammonemia, which can affect behavior and cognition. Eighteen percent of participants with ASS1D without documented hyperammonemic events self-reported lower attention spans, compared to 54% of participants with ASLD. More research into the unique neurocognitive characteristics of ASLD will help improve treatment and management.

Early prediction of phenotypic severity in Citrullinemia Type 1. Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Ann Clin Transl Neurol. 2019 Sep;6(9):1858-1871. doi: 10.1002/acn3.50886. Epub 2019 Aug 30.

Citrullinemia type1(ASS1D), also known as argininosuccinate synthase deficiency (ASS1D), is an inherited UCD that is detectable by newborn screening. The severity of the disease is variable, with health outcomes ranging from dangerous levels of hyperammonemic brain damage to mild, unnoticeable symptoms. Infant mortality rate for this disease has remained high over the decades despite the implementation of early treatment interventions. In this study, researchers evaluated a new test that could possibly predict the severity of ASS1D , based on the activity level of the enzyme argininosuccinate synthetase 1 (ASS1), which has been shown in previous studies to predict the severity of other inborn errors of metabolism. Participant data was collected from the Longitudinal Study of UCD conducted by the Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD). The researchers used a newly established assay to measure enzymatic activity of ASS1. The results showed that participants with ASS1D with ASS1 activity at 8.1% or lower experienced more frequent and severe hyperammonemic events and poorer cognitive function than participants with ASS1 activity above 8.1%. Additionally, participants with 26.6% or lower ASS1 activity had participated in special education programs, and those with 19.3% or lower ASS1 activity suffered more often from movement disorders. Participants with 4.8% or lower ASS1 activity were more likely to undergo liver transplantation. These results suggest that this enzymatic activity method could be useful in the clinical outcome prediction.

Hepatic arginase deficiency fosters dysmyelination during postnatal CNS development. Liu XB, Haney JR, Cantero G, Lambert JR, Otero-Garcia M, Truong B, Gropman A, Cobos I, Cederbaum SD, Lipshutz GS. JCI Insight. 2019 Sep 5;4(17):e130260. doi: 10.1172/jci.insight.130260.

Arginase deficiency is classified as a urea cycle disorder (UCD), as arginase is necessary in the breakdown of ammonia in the body. However, unlike other urea cycle disorders, hyperammonemia is uncommon with arginase deficiency. Complications that arise in this disorder such as paralysis, muscle stiffening, involuntary muscle contractions and overactive reflexes are also associated with cerebral palsy. Additionally, complications in arginase deficiency often occur later compared to other UCDs. In this study, researchers found that mice with arginase deficiency had abnormal myelin pattern in the brain and the spinal cord. Treatment of these arginase deficiency mice with arginase 1 gene therapy rescued these abnormal myelin patterns. Due to its unique characteristics among urea cycle disorders, the researchers suggest arginase deficiency be categorized as a leukodystrophy, a group of rare metabolic genetic disorders that affect the brain and spinal cord. This study did not label the cause of muscle and nerve failure within the disorder, yet supports the importance of ongoing neonatal screening, early intervention to normalize arginase production in the body. They also suggest that early postnatal liver-based gene therapy may be of use in preventing neurological abnormalities.

Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders. Posset R, Gropman AL, Nagamani SCS, Burrage LC, Bedoyan JK, Wong D, Berry GT, Baumgartner MR, Yudkoff M, Zielonka M, Hoffmann GF, Burgard P, Schulze A, McCandless SE, Garcia-Cazorla A, Seminara J, Garbade SF, Kölker S; Urea Cycle Disorders Consortium and the European Registry and Network for Intoxication Type Metabolic Diseases Consortia Study Group. Ann Neurol. 2019 Jul;86(1):116-128. doi: 10.1002/ana.25492. Epub 2019 May 13.

As intellectual and developmental disabilities are common in individuals diagnosed with urea cycle disorders (UCD), the purpose of this study was to evaluate the impact of diagnostic and treatment methods on cognitive outcomes such as thinking, reasoning, remembering, imagining, and learning. Results from neurocognitive testing of 503 individuals with UCD enrolled in the Longitudinal Study of UCD conducted by the UCD Consortium (UCDC) and the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD) from 2006 to 2016 were studied. IQ scores less than 70, indicating intellectual disability, were associated with UCD type and early disease onset. The height of initial peak plasma ammonium level was associated with poorer neurocognitive outcomes in proximal UCDs (CPS1, OTCD). Individuals with citrullinemia (argininosuccinate synthetase deficiency, ASS1D) and argininosuccinate lyase deficiency (ASLD) who were identified by newborn screening but did not have symptoms at diagnosis had better outcomes than those diagnosed after having symptoms. Additionally, early liver transplantation appeared to be beneficial.

Impairment of cognitive function in ornithine transcarbamylase deficiency is global rather than domain-specific and is associated with disease onset, sex, maximum ammonium, and number of hyperammonemic events. Buerger C, Garbade SF, Dietrich Alber F, Waisbren SE, McCarter R, Kölker S, Burgard P; Urea Cycle Disorders Consortium. J Inherit Metab Dis. 2019 Mar;42(2):243-253. doi: 10.1002/jimd.12013. Epub 2019 Jan 22.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder (UCD). OTCD presents with a wide range of symptom severity. In this study, the number of hyperammonaemic events, clinical findings, and cognitive functioning domains—intelligence (IQ), executive function, memory, visuomotor integration and visual perception—were compared across groups. The groups were separated according to disease onset type— late disease onset (clinical symptoms at more than 28 days old), early disease onset (clinical symptoms at 28 days old or less), or asymptomatic—sex, and age. Participant information collected by the Urea Cycle Disorders Consortium (UCDC) through the Longitudinal Study between 2006 and 2014 served as the data source, to include 300 OTCD participants who underwent psychological evaluations. Although mean scores of late onset and asymptomatic individuals were within 1 SD of the population norm (IQ = 85-115, which is the normal range for individuals with-out UCD, as well), asymptomatic participants attained significantly higher scores than late onset participants and males scored higher than females. Intelligence scores proved to correlate with overall cognitive functioning. The correlation between maximum ammonia concentration and intelligence correlated significantly higher in early onset than in late onset participants (i.e. higher ammonia levels correlated with lower IQ). Correlation between the number of hyperammonemic events and intelligence scores were similar for early onset and late onset individuals. The number of clinical symptoms was significantly associated with intelligence, but not with scores in other domains. Results suggest that OTCD has a global impact on cognitive functioning rather than a specific effect on distinct cognitive domains (executive function, memory, visual-motor integration, visual perception).

Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients. Diaz GA, Schulze A, Longo N, Rhead W, Feigenbaum A, Wong D, Merritt JL 2nd, Berquist W, Gallagher RC, Bartholomew D, McCandless SE, Smith WE, Harding CO, Zori R, Lichter-Konecki U, Vockley J, Canavan C, Vescio T, Holt RJ, Berry SA. Mol Genet Metab. 2019 Jul 10. pii: S1096-7192(19)30323-3. PMID: 31326288. Full Text.

Neuropsychological attributes of urea cycle disorders: A systematic review of the literature. Waisbren SE, Stefanatos AK, Kok TMY, Ozturk-Hismi B. J Inherit Metab Dis. 2019 Jul 3. PMID: 31268178, Full Text.

The m.11778 A > G variant associated with the coexistence of Leber's hereditary optic neuropathy and multiple sclerosis-like illness dysregulates the metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. Uittenbogaard M, Brantner CA, Fang Z, Wong LJ, Gropman A, Chiaramello A. Mitochondrion. 2019 May;46:187-194. doi: 10.1016/j.mito.2018.06.001. Epub 2018 Jun 8.

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases. Posset R, Garbade SF, Boy N, Burlina AB, Dionisi-Vici C, Dobbelaere D, Garcia-Cazorla A, de Lonlay P, Teles EL, Vara R, Mew NA, Batshaw ML, Baumgartner MR, McCandless SE, Seminara J, Summar M, Hoffmann GF, Kölker S, Burgard P; Additional individual contributors of the UCDC and the E-IMD consortium. J Inherit Metab Dis. 2019 Jan;42(1):93-106. doi: 10.1002/jimd.12031.

Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders. Burrage LC, Thistlethwaite L, Stroup BM, Sun Q, Miller MJ, Nagamani SCS, Craigen W, Scaglia F, Sutton VR, Graham B, Kennedy AD; Members of the UCDC,, Milosavljevic A, Lee BH, Elsea SH. Genet Med. 2019 Sep;21(9):1977-1986. doi: 10.1038/s41436-019-0442-0. Epub 2019 Jan 23.

Urea cycle disorders (UCDs) are screened and diagnosed through the use of biochemical and molecular testing. If biomarkers of UCDs, such as elevated (higher) levels of ammonia and arginine, are present in a patient’s screening tests, an analysis of their genetic composition (makeup) will confirm the disorder. However, this may not be a reliable method of diagnosis in all cases, as ornithine transcarbamylase deficiency (OTCD) can be difficult to identify due to the nature of the disorder. Untargeted metabolomic profiling has become an important tool in diagnosis and management of UCDs because it is able to detect biomarkers of UCDs that might not be captured by the traditional methods of diagnosis. In this study, samples from 48 subjects that were collected during routine clinical visits and samples from the Urea Cycle Disorders Consortium (UCDC) Longitudinal Study were analyzed with metabolomic profiling. Results from the analyses found known biomarkers of UCDs.

"Cerebral palsy" in a patient with arginase deficiency. Jichlinski A, Clarke L, Whitehead MT, Gropman A. Semin Pediatr Neurol. 2018;26:110-114. Full Text.

A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers. Nagamani SCS, Agarwal U, Tam A, Azamian M, McMeans A, Didelija IC, Mohammad MA, Marini JC. Genet Med. 2018 Jul;20(7):708-716. doi: 10.1038/gim.2017.167. Epub 2017 Oct 12.

Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension. Kho J, Tian X, Wong WT, Bertin T, Jiang MM, Chen S, Jin Z, Shchelochkov OA, Burrage LC, Reddy AK, Jiang H, Abo-Zahrah R, Ma S, Zhang P, Bissig KD, Kim JJ, Devaraj S, Rodney GG, Erez A, Bryan NS, Nagamani SCS, Lee BH. Am J Hum Genet. 2018 Aug 2;103(2):276-287. doi: 10.1016/j.ajhg.2018.07.008.

Key Point: A chemical deficiency associated with ASLD often leads to high blood pressure. Nitric oxide supplementation is currently being investigated in clinical trials as a treatment option for individuals with ASLD. In this study, the investigators used mice with argininosuccinate lyase deficiency (ASLD) and cells from patients with ASLD to study the mechanisms involved in causing high blood pressure in this disorder, which is the second most common UCD (Figure 4). The investigators show that loss of the urea cycle enzyme ASL in the lining cells of the blood vessels leads to reduction of a chemical called nitric oxide (NO) and an increase in oxidative stress that lead to vascular dysfunction. Using data from a human trial that was funded by the Urea Cycle Disorders Consortium (UCDC), they also show that the blood pressure in individuals with ASLD can be elevated. The results of this study can have potential treatment implications. Currently, nitric oxide supplementation is being investigated in clinical trials as a treatment option for individuals with ASLD.

Biochemical markers and neuropsychological functioning in distal urea cycle disorders. Waisbren SE, Cuthbertson D, Burgard P, Holbert A, McCarter R, Cederbaum S; Members of the Urea Cycle Disorders Consortium. J Inherit Metab Dis. 2018 Jul;41(4):657-667. doi: 10.1007/s10545-017-0132-5. Epub 2018 Feb 8.

The urea cycle breaks down ammonia into urea, which is then excreted (released) through urine; urea cycle disorders (UCDs) occur when a step in the urea cycle process is disrupted. Ammonia accumulation is shared amongst the different UCD types, but each individual UCD can have distinctive (unique) effects on the body. This report examines links between biochemical markers (ammonia, glutamine, arginine, citrulline) and neuropsychological test results in three UCD subtypes - argininosuccinic acid synthetase deficiency (ASD or citrullinemia type I), argininosuccinic acid lyase deficiency (ASA or ALD), and arginase deficiency (ARGD). Using data previously collected by the Urea Cycle Disorders Consortium’s Longitudinal Study, the investigators evaluated the neuropsychological tests and lab results of 145 participants (Figure 2). The neurological tests measured for intelligence (IQ), verbal and visual abilities, motor function and memory. As a result, the mean full scale IQ was below the population mean of 100 ± 15 for all groups: (ASD = 79 ± 24; ASA = 71 ± 21; ARGD = 65 ± 19), and the greatest deficits were noted in visual performance and motor skills for all groups. The biomarkers that most reliably indicated poor overall neuropsychological performance were ammonia and citrulline for ASD participants; ammonia, glutamine, and citrulline for ASA participants; and arginine, ammonia and citrulline for ARGD participants. Recognizing biomarker profiles is useful in deter-mining the most appropriate treatments.

Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium. Ah Mew N, Cnaan A, McCarter R, Choi H, Glass P, Rice K, Scavo L, Gillespie CW, Diaz GA, Berry GT, Wong D, Konczal L, McCandless SE, Coughlin CR, II, Weisfeld-Adams JD, Ficicioglu C, Yudkoff M, Enns GM, Lichter-Konecki U, Gallagher R, Tuchman M. Ah Mew N, Cnaan A, McCarter R, Choi H, Glass P, Rice K, Scavo L, Gillespie CW, Diaz GA, Berry GT, Wong D, Konczal L, McCandless SE., Coughlin CR, II, Weisfeld-Adams JD, Ficicioglu C, Yudkoff M, Enns GM, Lichter-Konecki U, Gallagher R, Tuchman M. Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium. Translational Science of Rare Diseases. 2018; 3: 157–170.

Inborn errors of metabolism (IEMs), such as urea cycle disorders (UCDs), fall within the category of ultra-rare disorders in which 1 in 50,000 people have the disorder, many of whom die during childhood. This publication focuses on the challenges the N-carbamylglutamate Consortium (NCGC) faced while conducting two trials for N-carbamylglutamate (NCG), an approved treatment for N-acetylglutamate synthetase (NAGS) deficiency, one of the UCD subtypes that causes hyperammonemia. Among the topics discussed is the difficulty of recruiting and retaining eligible participants; enrollment numbers are largely affected by the small participant selection pools characteristic of rare diseases and missed opportunities to refer patients to open studies during routine clinical visits. It is preferable to enroll participants during non-crisis situations in order to avoid an exaggeration of the expected number of hyperammonemia events that could occur during a study. Partnerships with patient advocacy groups such as the National Urea Cycle Disorders Foundation (NUCDF) are crucial for rare disease studies as they pro-vide opportunities for researchers to educate and reach out to potential participants and their families and caregivers. Introspective publications such as this are valuable in the evaluation and improvement of study methods.

Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells. Uittenbogaard M, Brantner CA, Chiaramello A. Cell Death Dis. 2018 Mar 2;9(3):360. doi: 10.1038/s41419-018-0396-1.

Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders. Meyburg J, Opladen T, Spiekerkötter U, Schlune A, Schenk JP, Schmidt J, Weitz J, Okun J, Bürger F, Omran TB, Abdoh G, Al Rifai H, Monavari A, Konstantopoulou V, Kölker S, Yudkoff M, Hoffmann GF. J Inherit Metab Dis. 2018;41:81-90. PMID: 29027067.

Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening. Merritt JL 2nd, Brody LL, Pino G, Rinaldo P. Mol Genet Metab. 2018 Jun;124(2):109-113. doi: 10.1016/j.ymgme.2018.04.006. Epub 2018 Apr 20. PubMed PMID: 29703588.

Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. Uittenbogaard M, Brantner CA, Fang Z, Wong LC, Gropman A, Chiaramello A. Mol Genet Metab. 2018 May;124(1):71-81. doi: 10.1016/j.ymgme.2018.03.011. Epub 2018 Mar 27.

Novel metabolic signatures of compound heterozygous Szt2 variants in a case of early-onset of epileptic encephalopathy. Uittenbogaard M, Gropman A, Brantner CA, Chiaramello A. Clin Case Rep. 2018 Oct 25;6(12):2376-2384. doi: 10.1002/ccr3.1868. eCollection 2018 Dec.

The utility of EEG monitoring in neonates with hyperammonemia due to inborn errors of metabolism. Wiwattanadittakul N, Prust M, Gaillard WD, Massaro A, Vezina G, Tsuchida TN, Gropman AL. Mol Genet Metab. 2018 Nov;125(3):235-240. doi: 10.1016/j.ymgme.2018.08.011. Epub 2018 Aug 24.

Continuous video electroencephalogram (cvEEG) is the long-term video monitoring of electrical activity in the brain. The typical length of an electroencephalogram (EEG) test is between 30 to 60 minutes, where as a cvEEG test can last for days at a time. Most infant seizures do not have clinical symptoms and can only be detected by an EEG, making cvEEG the preferred method for monitoring seizures associated with acute brain injury; however, the benefits of using cvEEG on infants with in-born errors of metabolism have not been determined. In this study, researchers analyzed the medical records of eight infants who experienced hyperammonemia due to inborn errors of metabolism and received prolonged EEG tests at Children's National Medical Center, Washington, D.C., between January 2009 and March 2017. The results showed that seven of the infants had seizures, and six had seizures that could only be detected by EEG. Although there was evidence that elevated levels of blood ammonia and glutamine—common symptoms of urea cycle disorders—had a possible connection to seizure activity on EEG, it is important to note that some of the infants, after receiving medication that normalized their blood ammonia and glutamine levels, continued to have seizures (Figure 5). Seizures were also detected by EEG before blood ammonia levels spiked and occurred within 24 to 36 hours of clinical symptoms. These and other findings documented in the study suggest the importance of long-term cvEEG in the evaluation of inborn errors of metabolism.

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders – a successful strategy for clinical research of rare diseases. Posset R, Garbade SF, Boy N, Burlina AB, Dionisi-Vici C, Dobbelaere D, Garcia-Cazorla A, de Lonlay P, Teles EL, Vara R, Ah Mew N, Batshaw ML, Baumgartner MR, McCandless SE, Seminara J, Summar ML, Hoffmann GF, Kölker S, Burgard P; on behalf of the UCDC and the E-IMD consortium. J Inherit Metab Dis. 2018 Jul 4. PMID: 29974348.

The Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication Type Metabolic Disorders (E-IMD) collaborated to compare the prevalence and characteristics of urea cycle disorders (UCDs) in North America and Europe. The UCDC Longitudinal Study data was used for North America. Combining registries from both consortia, researchers looked at the medical histories of over 1,000 patients with UCD for information such as UCD type, late disease onset (clinical symptoms at more than 28 days old) or early dis-ease onset (clinical symptoms at 28 days old or less), and age of diagnosis. In North America and Europe, Ornithine Transcarbamylase Deficiency (OTCD ) and late disease onset were the most common; however, the lack of early onset reports may have been caused by the voluntary nature of the registries, as the severe symptoms associated with early onset UCDs could make participation more difficult. The data also showed that the delay between age of clinical symptoms and age of diagnosis was shorter for early onset patients, which was likely due to the higher visibility of symptoms such as seizures.

Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice. Sin YY, Ballantyne LL, Richmond CR, Funk CD. Mol Ther Nucleic Acids. 2018 Mar 2;10:122-130. doi: 10.1016/j.omtn.2017.11.012. Epub 2017 Dec 1.

This study, funded by a Urea Cycle Disorders Consortium (UCDC) training grant, focused on the possibility of incorporating gene editing in a preclinical animal model for treatment of urea cycle disorder (UCD), specifically arginase deficiency. Induced pluripotent stem cells (iPSCs), or cells that can become any type of cell in the body, were turned into hepatocyte-like cells (HLCs), or liver cells. The HLCs were transplanted into mice with arginase deficiency, and investigators monitored the mice for signs that the HLCs were producing arginase enzyme. The results showed 5% liver regeneration, low productions of arginase, and a maximum lifespan of 22 days compared to 14 days in arginase-deficient mice that were not trans-planted. Although the initial proof of concept study showed minimal improvements, the research suggests that there might be a place for such therapies in the future.

Urea Cycle Disorders. *Lindsay C, Burrage, Brendan Lee, and Sandesh C, S Nagamani. Rudolph Pediatrics, Chapter 141, p 23rd Edition, McGraw Hill, 2018.

Glycerol phenylbutyrate for the maintenance treatment of patients with deficiencies in enzymes of the urea cycle. Longo N , Holt RJ. Expert Opin. on Orphan Drugs, 5 (12) (2017), pp. 999-1010. Full Text.

Hyperammonemia in Neonates: Looking beyond sepsis. Schrier Vergano SA, Le Mons C. Neonatology Today 2017 Dec, Vol 13/Issue 12, pp 15-16. Online Full Text.

Incidence, disease onset and short-term outcome in urea cycle disorders -cross-border surveillance in Germany, Austria and Switzerland. Nettesheim S, Kölker S, Karall D, Häberle J, Posset R, Hoffmann GF, Heinrich B, Gleich F, Garbade SF; Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU). Orphanet J Rare Dis. 2017;12:111. PMID: 28619060, PMCID: PMC5472961.

Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes. Shi D, Zhao G, Ah Mew N, Tuchman M. Mol Genet Metab. 2017 Mar;120(3):198–206. PMID: 28007335, PMCID: PMC5346444.

Proof-of-Concept Gene Editing for the Murine Model of Inducible Arginase-1 Deficiency. Sin YY, Price PR, Ballantyne LL, Funk CD. Sci Rep. 2017 May 31;7(1):2585. doi: 10.1038/s41598-017-02927-2.

Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2 months to 2 years. Berry SA, Longo N, Diaz GA, McCandless SE, Smith WE, Harding CO, Zori R, Ficicioglu C, Lichter-Konecki U, Robinson B, Vockley J. Mol Genet Metab. 2017;122(3):46-53. PMID: 28916119, Full Text.

Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders. Posset R, Garcia-Cazorla A, Valayannopoulos V, Teles EL, Dionisi-Vici C, Brassier A, Burlina AB, Burgard P, Cortès-Saladelafont E, Dobbelaere D, Couce ML, Sykut-Cegielska J, Häberle J, Lund AM, Chakrapani A, Schiff M, Walter JH, Zeman J, Vara R, Kölker S, additional individual contributors of the E-IMD consortium. J Inherit Metab Dis. 2016;39:661-672. PMID: 27106216.

Barriers to drug adherence in the treatment of urea cycle disorders: assessment of patient, caregiver and provider perspectives. Shchelochkov OA ,Dickinson K , Scharschmidt BF , Lee B, Marino M, Le Mons C. Mol Genet and Metab Rep., 8 (2016 Sep), pp. 43-47. PMID: 27493880,  PMCID: PMC4963256.

Behavioural and emotional problems, intellectual impairment and health-related quality of life in patients with organic acidurias and urea cycle disorders. Jamiolkowski D, Kölker S, Glahn EM, Barić I, Zeman J, Baumgartner MR, Mühlhausen C, Garcia-Cazorla A, Gleich F, Haege G, Burgard P; E-IMD consortium. J Inherit Metab Dis. 2016; 39: 231-41. PMID: 26310964.

Brain biomarkers and neuroimaging to diagnose urea cycle disorders and assess prognosis. Barkovich E, Robinson C, Gropman A. Expert Opinion on Orphan Drugs, 4:11, 1123-1132. Abstract.

Elevations of C14:1 and C14:2 Plasma Acylcarnitines in Fasted Children: A Diagnostic Dilemma. Burrage LC, Miller MJ, Wong LJ, Kennedy AD, Sutton VR, Sun Q, Elsea SH, Graham BH. J Pediatr. 2016 Feb;169:208-13.e2. doi: 10.1016/j.jpeds.2015.10.045. Epub 2015 Nov 18.

Executive functioning profiles from the BRIEF across pediatric medical disorders: Age and diagnosis factors. Krivitzky LS, Walsh KS, Fisher EL, Berl MM. Child Neuropsychol. 2016;22(7):870-88. doi: 10.1080/09297049.2015.1054272. Epub 2015 Jul 6.

Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD). Laemmle A, Gallagher RC, Keogh A, Stricker T, Gautschi M, Nuoffer JM, Baumgartner MR, Häberle J. PLoS One. 2016 Apr 12;11(4):e0153358. doi: 10.1371/journal.pone.0153358. eCollection 2016.

Glutamine and hyperammonemic crises in patients with urea cycle disorders. Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA, Le Mons C, Bartley J, Longo N, Nagamani SC, Berquist W, Gallagher RC, Harding CO, McCandless SE, Smith W, Schulze A, Marino M, Rowell R, Coakley DF, Mokhtarani M, Scharschmidt BF. Mol Genet Metab. 2016 Jan;117(1):27-32. doi: 10.1016/j.ymgme.2015.11.005. Epub 2015 Nov 11.

Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment. Butler MG, Lee J, Cox DM, Manzardo AM, Gold JA, Miller JL, Roof E, Dykens E, Kimonis V, Driscoll DJ. Clin Pediatr (Phila). 2016 Sep;55(10):957-74. doi: 10.1177/0009922815617973. Epub 2016 Feb 3.

Improving long term outcomes in urea cycle disorders-report from the Urea Cycle Disorders Consortium. Waisbren SE, Gropman AL; Members of the Urea Cycle Disorders Consortium (UCDC), Batshaw ML. J Inherit Metab Dis. 2016 Jul;39(4):573-84. doi: 10.1007/s10545-016-9942-0. Epub 2016 May 23.

In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis. Opladen T, Lindner M, Das AM, Marquardt T, Khan A, Emre SH, Burton BK, Barshop BA, Böhm T, Meyburg J, Zangerl K, Mayorandan S, Burgard P, Dürr UH, Rosenkranz B, Rennecke J, Derbinski J, Yudkoff M, Hoffmann GF. Mol Genet Metab. 2016 Jan;117(1):19-26. doi: 10.1016/j.ymgme.2015.11.007. Epub 2015 Nov 14.

Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions. Shapiro E, Bernstein J, Adams HR, Barbier AJ, Buracchio T, Como P, Delaney KA, Eichler F, Goldsmith JC, Hogan M, Kovacs S, Mink JW, Odenkirchen J, Parisi MA, Skrinar A, Waisbren SE, Mulberg AE. Mol Genet Metab. 2016 Jun;118(2):65-9. doi: 10.1016/j.ymgme.2016.04.006. Epub 2016 Apr 14.

Nineteen-year follow-up of a patient with severe glutathione synthetase deficiency. Atwal PS, Medina CR, Burrage LC, Sutton VR. J Hum Genet. 2016 Jul;61(7):669-72. doi: 10.1038/jhg.2016.20. Epub 2016 Mar 17.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Arginase-1 deficiency. *Sin YY, Baron G, Schulze A, Funk CD. J Mol Med (Berl). 2015 Dec;93(12):1287-96. PMID: 26467175.

Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3. Chong JX, Burrage LC, Beck AE, Marvin CT, McMillin MJ, Shively KM, Harrell TM, Buckingham KJ, Bacino CA, Jain M, Alanay Y, Berry SA, Carey JC, Gibbs RA, Lee BH, Krakow D, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ. Am J Hum Genet. 2015 May 7;96(5):841-9. doi: 10.1016/j.ajhg.2015.04.004.

Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA, Le Mons C, Bartley JA, Longo N, Nagamani SC, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Cederbaum S, Wong D, Merritt JL 2nd, Schulze A, Vockley J, Kronn D, Zori R, Summar M, Milikien DA, Marino M, Coakley DF, Mokhtarani M; UCD Consortium, Scharschmidt BF. Genet Med. 2015 Jul;17(7):561-8. doi: 10.1038/gim.2014.148. Epub 2014 Dec 11.

Catel-Manzke Syndrome: Further Delineation of the Phenotype Associated with Pathogenic Variants in TGDS. Pferdehirt R, Jain M, Blazo MA, Lee B, Burrage LC. Mol Genet Metab Rep. 2015 Sep 1;4:89-91. doi: 10.1016/j.ymgmr.2015.08.003.

De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Burrage LC, Charng WL, Eldomery MK, Willer JR, Davis EE, Lugtenberg D, Zhu W, Leduc MS, Akdemir ZC, Azamian M, Zapata G, Hernandez PP, Schoots J, de Munnik SA, Roepman R, Pearring JN, Jhangiani S, Katsanis N, Vissers LE, Brunner HG, Beaudet AL, Rosenfeld JA, Muzny DM, Gibbs RA, Eng CM, Xia F, Lalani SR, Lupski JR, Bongers EM, Yang Y. Am J Hum Genet. 2015 Dec 3;97(6):904-13. doi: 10.1016/j.ajhg.2015.11.006.

From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases. Shi D, Allewell NM, Tuchman M. Int J Mol Sci. 2015 Aug 12;16(8):18836-64. doi: 10.3390/ijms160818836.

Genotype-Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update. Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H. J Genet Genomics. 2015 May 20;42(5):181-94. doi: 10.1016/j.jgg.2015.04.003. Epub 2015 May 19.

Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency. Burrage LC, Sun Q, Elsea SH, Jiang MM, Nagamani SC, Frankel AE, Stone E, Alters SE, Johnson DE, Rowlinson SW, Georgiou G; Members of Urea Cycle Disorders Consortium, Lee BH. Hum Mol Genet. 2015 Nov 15;24(22):6417-27. doi: 10.1093/hmg/ddv352. Epub 2015 Sep 10.

Impact of age at onset and newborn screening on outcome in organic acidurias. Heringer J, Valayannopoulos V, Lund AM, Wijburg FA, Freisinger P, Barić I, Baumgartner MR, Burgard P, Burlina AB, Chapman KA, I Saladelafont EC, Karall D, Mühlhausen C, Riches V, Schiff M, Sykut-Cegielska J, Walter JH, Zeman J, Chabrol B, Kölker S, additional individual contributors of the E-IMD consortium. J Inherit Metab Dis. 2015 Dec 21. PMID: 26689403, Full Text (with PubMed access).

Inherited Metabolic Disorders: Aspects of Chronic Nutrition Management. Boyer SW, Barclay LJ, Burrage LC. Nutr Clin Pract. 2015 Aug;30(4):502-10. doi: 10.1177/0884533615586201. Epub 2015 Jun 16.

Networking across borders for individuals with organic acidurias and urea cycle disorders: The E-IMD Consortium. Kolker S, Dobbelaere D, Haberle J, Burgard P, Gleich F, Summar ML, Hannigan S, Parker S, Chakrapani A, Baumgartner MR, and on behalf of the E-IMD Consortium. JIMD Reports. 2015;22:29-38. PMID: 25701269, PMCID: PMC4486274.

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Miller MJ, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ. Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency. Pacheco-Colón I, Washington SD, Sprouse C, Helman G, Gropman AL, VanMeter JW. PLoS One. 2015 Jun 11;10(6):e0129595. doi: 10.1371/journal.pone.0129595. eCollection 2015.

Role of brain imaging for demonstrating ammonia-induced changes. Pacheco-Colón Ileana, Fricke Stanley and Gropman Andrea. In Current Approach to Hyperammonemia. Johannes Häberle (ed). eBook, Future Medicine. 2014.

Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. Nagamani SC, Diaz GA, Rhead W, Berry SA, Le Mons C, Lichter-Konecki U, Bartley J, Feigenbaum A, Schulze A, Longo N, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Vockley J, Kronn D, Zori R, Cederbaum S, Merritt JL 2nd, Wong D, Coakley DF, Scharschmidt BF, Dickinson K, Marino M, Lee BH, Mokhtarani M. Mol Genet Metab. 2015 Sep-Oct;116(1-2):29-34. doi: 10.1016/j.ymgme.2015.08.002. Epub 2015 Aug 5.

Strategies to rescue the consequences of inducible arginase-1 deficiency in mice. *Ballantyne LL, Sin YY, St Amand T, Si J, Goossens S, Haenebalcke L, Haigh JJ, Kyriakopoulou L, Schulze A, Funk CD. PLoS One. 2015 May 4;10(5):e0125967. PMID: 25938595, PMCID: PMC4418594.

Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate. Zhao G, Jin Z, Allewell NM, Tuchman M, Shi D. Acta Crystallogr F Struct Biol Commun. 2015 Jan 1;71(Pt 1):86-95. doi: 10.1107/S2053230X14026788. Epub 2015 Jan 1.

The N-Acetylglutamate Synthase Family: Structures, Function and Mechanisms. Shi D, Allewell NM, Tuchman M. Int J Mol Sci. 2015 Jun 9;16(6):13004-22. doi: 10.3390/ijms160613004.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. Kolker S, Garcia-Cazorla A, Valayannopoulos V, Lund AM, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Barić I, Karall D, Augoustides-Savvopoulou P, Aksglaede L, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Chabrol B, Chakrapani A, Chapman K, I Saladelafont EC, Couce ML, de Meirleir L, Dobbelaere D, Dvorakova V, Furlan F, Gleich F, Gradowska W, Grünewald S, Jalan A, Häberle J, Haege G, Lachmann R, Laemmle A, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, de Baulny HO, Ortez C, Peña-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Staufner C, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Burgard P. J Inherit Metab Dis. 2015 Nov;38(6):1041-1057. PMID: 25875215, Full Text  (with PubMed access).

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. Kolker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Barić I, Karall D, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Boy SP, Rasmussen MB, Burgard P, Chabrol B, Chakrapani A, Chapman K, Cortès I Saladelafont E, Couce ML, de Meirleir L, Dobbelaere D, Furlan F, Gleich F, González MJ, Gradowska W, Grünewald S, Honzik T, Hörster F, Ioannou H, Jalan A, Häberle J, Haege G, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, Murphy E, de Baulny HO, Ortez C, Pedrón CC, Pintos-Morell G, Pena-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Lund AM, Garcia-Cazorla A. J Inherit Metab Dis. 2015 Nov;38(6):1059-1074. PMID: 25875216, Full Text (with PubMed access).

A longitudinal study of urea cycle disorders. Batshaw ML, Tuchman M, Summar M, Seminara J; Members of the Urea Cycle Disorders Consortium. Mol Genet Metab. 2014 Sep-Oct;113(1-2):127-30. doi: 10.1016/j.ymgme.2014.08.001. Epub 2014 Aug 10.

Advances in urea cycle neuroimaging: Proceedings from the 4th International Symposium on urea cycle disorders, Barcelona, Spain, September 2013. Pacheco-Colón I, Fricke S, VanMeter J, Gropman AL. Mol Genet Metab. 2014 Sep-Oct;113(1-2):118-26. doi: 10.1016/j.ymgme.2014.05.005. Epub 2014 May 20.

Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1 deficiency with N-carbamyl-L-glutamate. Ah Mew N, McCarter R, Daikhin Y, Lichter-Konecki U, Nissim I, Yudkoff M, Tuchman M. J Pediatr. 2014 Aug;165(2):401-403.e3. doi: 10.1016/j.jpeds.2014.04.012. Epub 2014 May 29.

Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders. Burrage LC, Nagamani SC, Campeau PM, Lee BH. Hum Mol Genet. 2014 Sep 15;23(R1):R1-8. doi: 10.1093/hmg/ddu123. Epub 2014 Mar 20.

Expression pattern and biochemical properties of zebrafish N-acetylglutamate synthase. Caldovic L, Haskins N, Mumo A, Majumdar H, Pinter M, Tuchman M, Krufka A. PLoS One. 2014 Jan 22;9(1):e85597. doi: 10.1371/journal.pone.0085597. eCollection 2014.

Genomics in newborn screening. Landau YE, Lichter-Konecki U, Levy HL. J Pediatr. 2014 Jan;164(1):14-9. doi: 10.1016/j.jpeds.2013.07.028. Epub 2013 Aug 27.

Glycerol phenylbutyrate treatment in children with urea cycle disorders: pooled analysis of short and long-term ammonia control and outcomes. Berry SA, Lichter-Konecki U, Diaz GA, McCandless SE, Rhead W, Smith W, Lemons C, Nagamani SC, Coakley DF, Mokhtarani M, Scharschmidt BF, Lee B. Mol Genet Metab. 2014 May;112(1):17-24. doi: 10.1016/j.ymgme.2014.02.007. Epub 2014 Feb 21.

Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency. Sprouse C, King J, Helman G, Pacheco-Colón I, Shattuck K, Breeden A, Seltzer R, VanMeter JW, Gropman AL. Mol Genet Metab. 2014 Sep-Oct;113(1-2):136-41. doi: 10.1016/j.ymgme.2014.05.007. Epub 2014 May 20.

Research into rare diseases of childhood. Batshaw ML, Groft SC, Krischer JP. JAMA. 2014 May 7;311(17):1729-30. doi: 10.1001/jama.2013.285873.

Significant hepatic involvement in patients with ornithine transcarbamylase deficiency. Gallagher RC, Lam C, Wong D, Cederbaum S, Sokol RJ. J Pediatr. 2014 Apr;164(4):720-725.e6. doi: 10.1016/j.jpeds.2013.12.024. Epub 2014 Jan 30.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders. Burrage LC, Jain M, Gandolfo L, Lee BH; Members of the Urea Cycle Disorders Consortium, Nagamani SC. Mol Genet Metab. 2014 Sep-Oct;113(1-2):131-5. doi: 10.1016/j.ymgme.2014.06.005. Epub 2014 Jul 3.

Stable isotopes in the diagnosis and treatment of inherited hyperammonemia. Mew NA, Yudkoff M, Tuchman M. J Pediatr Biochem. 2014 Jan 1;4(1):57-63. doi: 10.3233/JPB-140106.

The urea cycle disorders. Helman G, Pacheco-Colón I, Gropman AL. Semin Neurol. 2014 Jul;34(3):341-9. doi: 10.1055/s-0034-1386771. Epub 2014 Sep 5.

A decisional space for fMRI pattern separation using the principal component analysis--a comparative study of language networks in pediatric epilepsy. You X, Adjouadi M, Wang J, Guillen MR, Bernal B, Sullivan J, Donner E, Bjornson B, Berl M, Gaillard WD. Hum Brain Mapp. 2013 Sep;34(9):2330-42. doi: 10.1002/hbm.22069. Epub 2012 Mar 28.

A dynamical approach toward understanding mechanisms of team science: change, kinship, tension, and heritage in a transdisciplinary team. Lotrecchiano, GR. Clin Transl Sci. 2013 Aug;6(4): 267–278. PMID: 23919361, PMCID: PMC5350836.

Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: an fMRI study. Gropman AL, Shattuck K, Prust MJ, Seltzer RR, Breeden AL, Hailu A, Rigas A, Hussain R, VanMeter J. Hum Brain Mapp. 2013 Apr;34(4):753-61. doi: 10.1002/hbm.21470. Epub 2011 Nov 23.

Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, Longo N, Berquist W, Berry SA, Gallagher R, Lichter-Konecki U, Bartholomew D, Harding CO, Cederbaum S, McCandless SE, Smith W, Vockley G, Bart SA, Korson MS, Kronn D, Zori R, Merritt JL 2nd, C S Nagamani S, Mauney J, Lemons C, Dickinson K, Moors TL, Coakley DF, Scharschmidt BF, Lee B. Hepatology. 2013 Jun;57(6):2171-9. doi: 10.1002/hep.26058. Epub 2013 Jan 3.

Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Smith W, Diaz GA, Lichter-Konecki U, Berry SA, Harding CO, McCandless SE, LeMons C, Mauney J, Dickinson K, Coakley DF, Moors T, Mokhtarani M, Scharschmidt BF, Lee B. J Pediatr. 2013 Jun;162(6):1228-34, 1234.e1. doi: 10.1016/j.jpeds.2012.11.084. Epub 2013 Jan 13.

Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ. Ah Mew N, Krivitzky L, McCarter R, Batshaw M, Tuchman M; Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research Network. J Pediatr. 2013 Feb;162(2):324-9.e1. doi: 10.1016/j.jpeds.2012.06.065. Epub 2012 Aug 15.

Crystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms. Zhao G, Jin Z, Allewell NM, Tuchman M, Shi D. PLoS One. 2013 Jul 24;8(7):e70369. doi: 10.1371/journal.pone.0070369. Print 2013.

Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion. Tuchman S, Asico LD, Escano C, Bobb DA, Ray PE. Pediatr Res. 2013 Feb;73(2):194-200. doi: 10.1038/pr.2012.172. Epub 2012 Nov 22.

Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Mol Genet Metab. 2013 Dec;110(4):446-53. doi: 10.1016/j.ymgme.2013.09.017. Epub 2013 Oct 8.

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias. Lichter-Konecki U, Nadkarni V, Moudgil A, Cook N, Poeschl J, Meyer MT, Dimmock D, Baumgart S. Mol Genet Metab. 2013 Aug;109(4):354-9. doi: 10.1016/j.ymgme.2013.05.014. Epub 2013 May 29.

Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism. *Sin YY, Ballantyne LL, Mukherjee K, St Amand T, Kyriakopoulou L, Schulze A, Funk CD. PLoS One. 2013;8(11):e80001. PMID: 24224027, PMCID: PMC3817112.

Infectious precipitants of acute hyperammonemia are associated with indicators of increased morbidity in patients with urea cycle disorders. McGuire PJ, Lee HS; members of the Urea Cycle Disorders Consoritum, Summar ML. J Pediatr. 2013 Dec;163(6):1705-1710.e1. doi: 10.1016/j.jpeds.2013.08.029. Epub 2013 Sep 29.

Magnetic resonance imaging findings and neurodevelopmental outcomes in neonates with urea-cycle defects. Gunz AC, Choong K, Potter M, Miller E. Int Med Case Rep J., 6 (2013 08/19), pp. 41-48. PMID: 23983495, PMCID: PMC3751504.

Ornithine Transcarbamylase Deficiency. Lichter-Konecki U, Caldovic L, Morizono H, Simpson K. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. 2013 Aug 29. PMID: 24006547, Full Text.

Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986.

Population pharmacokinetic modeling and dosing simulations of nitrogen-scavenging compounds: disposition of glycerol phenylbutyrate and sodium phenylbutyrate in adult and pediatric patients with urea cycle disorders. Monteleone JP, Mokhtarani M, Diaz GA, Rhead W, Lichter-Konecki U, Berry SA, Lemons C, Dickinson K, Coakley D, Lee B, Scharschmidt BF. J Clin Pharmacol. 2013 Jul;53(7):699-710. doi: 10.1002/jcph.92. Epub 2013 Jun 15.

Recurrent encephalopathy: NAGS (N-acetylglutamate synthase) deficiency in adults. Cartagena A, Prasad AN, Rupar CA, Strong M, Tuchman M, Ah Mew N, Prasad C. Can J Neurol Sci. 2013 Jan;40(1):3-9. doi: 10.1017/s0317167100012877.

Structure of N-acetyl-L-glutamate synthase/kinase from Maricaulis maris with the allosteric inhibitor L-arginine bound. Zhao G, Haskins N, Jin Z, M Allewell N, Tuchman M, Shi D. Biochem Biophys Res Commun. 2013 Aug 9;437(4):585-90. doi: 10.1016/j.bbrc.2013.07.003. Epub 2013 Jul 10.

Structure of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog. Zhao G, Allewell NM, Tuchman M, Shi D. Biochem Biophys Res Commun. 2013 Jan 25;430(4):1253-8. doi: 10.1016/j.bbrc.2012.12.064. Epub 2012 Dec 20.

The incidence of urea cycle disorders. Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, Kirmse B; European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD) Electronic address: http://wwwe-imdorg/en/indexphtml; Members of the Urea Cycle Disorders Consortium (UCDC) Electronic address: http://rarediseasesnetworkepiusfedu/ucdc/. Mol Genet Metab. 2013 Sep-Oct;110(1-2):179-80. doi: 10.1016/j.ymgme.2013.07.008. Epub 2013 Jul 18.

Urea cycle defects and hyperammonemia: effects on functional imaging. Gropman AL, Prust M, Breeden A, Fricke S, VanMeter J. Metab Brain Dis. 2013 Jun;28(2):269-75. doi: 10.1007/s11011-012-9348-0. Epub 2012 Nov 13.

Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer. Zhong L, Li S, Li M, Xie J, Zhang Y, Lee B, Batshaw ML, Wilson JM, Gao G. Hum Gene Ther. 2013 Sep;24(9):814-9. doi: 10.1089/hum.2013.118.

A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria. Nagamani SC, Shchelochkov OA, Mullins MA, Carter S, Lanpher BC, Sun Q, Kleppe S, Erez A, O'Brian Smith E, Marini JC; Members of the Urea Cycle Disorders Consortium, Lee B. Mol Genet Metab. 2012 Nov;107(3):315-21. doi: 10.1016/j.ymgme.2012.09.016. Epub 2012 Sep 17.

Argininosuccinate lyase deficiency. Nagamani SC, Erez A, Lee B. Genet Med. 2012 May;14(5):501-7. doi: 10.1038/gim.2011.1. Epub 2012 Jan 5.

Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma. Payne AS, Freishtat RJ. J Investig Med. 2012 Jan;60(1):13-7. doi: 10.2310/JIM.0b013e31823d7989.

Hepatocellular carcinoma in a research subject with ornithine transcarbamylase deficiency. Wilson JM, Shchelochkov OA, Gallagher RC, Batshaw ML. Mol Genet Metab. 2012 Feb;105(2):263-5. doi: 10.1016/j.ymgme.2011.10.016. Epub 2011 Nov 7.

Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Nagamani SC, Campeau PM, Shchelochkov OA, Premkumar MH, Guse K, Brunetti-Pierri N, Chen Y, Sun Q, Tang Y, Palmer D, Reddy AK, Li L, Slesnick TC, Feig DI, Caudle S, Harrison D, Salviati L, Marini JC, Bryan NS, Erez A, Lee B. Am J Hum Genet. 2012 May 4;90(5):836-46. doi: 10.1016/j.ajhg.2012.03.018. Epub 2012 Apr 26.

Optimizing therapy for argininosuccinic aciduria. Nagamani SC, Lee B, Erez A. Mol Genet Metab. 2012 Sep;107(1-2):10-4. doi: 10.1016/j.ymgme.2012.07.009. Epub 2012 Jul 20.

Patterns of brain injury in inborn errors of metabolism. Gropman AL. Semin Pediatr Neurol. 2012 Dec;19(4):203-10. doi: 10.1016/j.spen.2012.09.007.

Peptide tyrosine tyrosine levels are increased in patients with urea cycle disorders. Mitchell S, Welch-Burke T, Dumitrescu L, Lomenick JP, Murdock DG, Crawford DC, Summar M. Mol Genet Metab. 2012 May;106(1):39-42. doi: 10.1016/j.ymgme.2012.02.011. Epub 2012 Feb 22.

Phase measurement of cognitive impairment specific to radiotherapy. Armstrong CL, Shera DM, Lustig RA, Phillips PC. Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):e319-24. doi: 10.1016/j.ijrobp.2011.12.083. Epub 2012 Mar 13.

Prolonged hypoxia augments L-citrulline transport by system A in the newborn piglet pulmonary circulation. Fike CD, Sidoryk-Wegrzynowicz M, Aschner M, Summar M, Prince LS, Cunningham G, Kaplowitz M, Zhang Y, Aschner JL. Cardiovasc Res. 2012 Aug 1;95(3):375-84. doi: 10.1093/cvr/cvs186. Epub 2012 Jun 6.

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders. Mokhtarani M, Diaz GA, Rhead W, Lichter-Konecki U, Bartley J, Feigenbaum A, Longo N, Berquist W, Berry SA, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Vockley J, Bart S, Kronn D, Zori R, Cederbaum S, Dorrani N, Merritt JL 2nd, Sreenath-Nagamani S, Summar M, Lemons C, Dickinson K, Coakley DF, Moors TL, Lee B, Scharschmidt BF. Mol Genet Metab. 2012 Nov;107(3):308-14. doi: 10.1016/j.ymgme.2012.08.006. Epub 2012 Aug 18.

Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Lichter-Konecki U, Diaz GA, Merritt JL 2nd, Feigenbaum A, Jomphe C, Marier JF, Beliveau M, Mauney J, Dickinson K, Martinez A, Mokhtarani M, Scharschmidt B, Rhead W. Mol Genet Metab. 2011 Aug;103(4):323-9. doi: 10.1016/j.ymgme.2011.04.013. Epub 2011 May 5.

Arginase I deficiency: severe infantile presentation with hyperammonemia: more common than reported?. Jain-Ghai S, Nagamani SC, Blaser S, Siriwardena K, Feigenbaum A. Mol Genet Metab. 2011 Sep-Oct;104(1-2):107-11. doi: 10.1016/j.ymgme.2011.06.025. Epub 2011 Jul 13.

Argininosuccinate Lyase deficiency. *Sandesh C Sreenath Nagamani,  Ayelet Erez, Brendan Lee. (February 2011): in GeneReviews: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. Seattle (WA): University of Washington, Seattle, 1993-2011 Feb 03. Featured e-book on NCBI Bookshelf, Full Text.

Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond. Erez A, Nagamani SC, Lee B. Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):45-53. doi: 10.1002/ajmg.c.30289. Epub 2011 Feb 10.

Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase. Nissim I, Horyn O, Nissim I, Daikhin Y, Caldovic L, Barcelona B, Cervera J, Tuchman M, Yudkoff M. J Biol Chem. 2011 Jun 24;286(25):22055-68. doi: 10.1074/jbc.M110.209023. Epub 2011 May 3.

Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Ünalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; Nonalcoholic Steatohepatitis Clinical Research Network. JAMA. 2011 Apr 27;305(16):1659-68. doi: 10.1001/jama.2011.520.

Energy prediction equations are inadequate for obese Hispanic youth. Klein CJ, Villavicencio SA, Schweitzer A, Bethepu JS, Hoffman HJ, Mirza NM. J Am Diet Assoc. 2011 Aug;111(8):1204-10. doi: 10.1016/j.jada.2011.05.010.

Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters. Stemmy EJ, Benton AS, Lerner J, Alcala S, Constant SL, Freishtat RJ. J Asthma. 2011 Dec;48(10):986-993. doi: 10.3109/02770903.2011.623334. Epub 2011 Oct 14.

Hepatitis B vaccination in HIV-infected youth: a randomized trial of three regimens. Flynn PM, Cunningham CK, Rudy B, Wilson CM, Kapogiannis B, Worrell C, Bethel J, Monte D, Bojan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). J Acquir Immune Defic Syndr. 2011 Apr;56(4):325-32. doi: 10.1097/QAI.0b013e318203e9f2.

Insights into the pathogenesis and treatment of cancer from inborn errors of metabolism. Erez A, Shchelochkov OA, Plon SE, Scaglia F, Lee B. Am J Hum Genet. 2011 Apr 8;88(4):402-21. doi: 10.1016/j.ajhg.2011.03.005.

Molecular characterization of CPS1 deletions by array CGH. Wang J, Shchelochkov OA, Zhan H, Li F, Chen LC, Brundage EK, Pursley AN, Schmitt ES, Häberle J, Wong LJ. Mol Genet Metab. 2011 Jan;102(1):103-6. doi: 10.1016/j.ymgme.2010.08.020. Epub 2010 Sep 19.

Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, Eeds A, Willis A, Yadav M, Summar S; Urea Cycle Disorders Consortium, Lichtarge O, Rubio V, Wong LJ, Summar M. Hum Mutat. 2011 Jun;32(6):579-89. doi: 10.1002/humu.21406. Epub 2011 May 5.

N-acetylglutamate synthase deficiency: an insight into the genetics, epidemiology, pathophysiology, and treatment. Ah Mew N, Caldovic L. Appl Clin Genet. 2011 Aug 24;4:127-35. doi: 10.2147/TACG.S12702. Print 2011.

N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy. Heibel SK, Ah Mew N, Caldovic L, Daikhin Y, Yudkoff M, Tuchman M. Hum Mutat. 2011 Oct;32(10):1153-60. doi: 10.1002/humu.21553. Epub 2011 Sep 9.

New frontiers in neuroimaging applications to inborn errors of metabolism. Prust MJ, Gropman AL, Hauser N. Mol Genet Metab. 2011 Nov;104(3):195-205. doi: 10.1016/j.ymgme.2011.06.020. Epub 2011 Jun 30.

Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children. Best BM, Capparelli EV, Diep H, Rossi SS, Farrell MJ, Williams E, Lee G, van den Anker JN, Rakhmanina N. J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):385-91. doi: 10.1097/QAI.0b013e318232b057.

Phenylbutyrate improves nitrogen disposal via an alternative pathway without eliciting an increase in protein breakdown and catabolism in control and ornithine transcarbamylase-deficient patients. Marini JC, Lanpher BC, Scaglia F, O'Brien WE, Sun Q, Garlick PJ, Jahoor F, Lee B. Am J Clin Nutr. 2011 Jun;93(6):1248-54. doi: 10.3945/ajcn.110.009043. Epub 2011 Apr 13.

Phenylbutyrate therapy for maple syrup urine disease. Brunetti-Pierri N, Lanpher B, Erez A, Ananieva EA, Islam M, Marini JC, Sun Q, Yu C, Hegde M, Li J, Wynn RM, Chuang DT, Hutson S, Lee B. Hum Mol Genet. 2011 Feb 15;20(4):631-40. doi: 10.1093/hmg/ddq507. Epub 2010 Nov 23.

Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, Gruchalla RS, Kattan M, Teach SJ, Pongracic JA, Chmiel JF, Steinbach SF, Calatroni A, Togias A, Thompson KM, Szefler SJ, Sorkness CA. N Engl J Med. 2011 Mar 17;364(11):1005-15. doi: 10.1056/NEJMoa1009705.

Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Nelson JE, Wilson L, Brunt EM, Yeh MM, Kleiner DE, Unalp-Arida A, Kowdley KV; Nonalcoholic Steatohepatitis Clinical Research Network. Hepatology. 2011 Feb;53(2):448-57. doi: 10.1002/hep.24038. Epub 2010 Nov 29.

Requirement of argininosuccinate lyase for systemic nitric oxide production. Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B. Nat Med. 2011 Nov 13;17(12):1619-26. doi: 10.1038/nm.2544.

Research challenges in central nervous system manifestations of inborn errors of metabolism. Dickson PI, Pariser AR, Groft SC, Ishihara RW, McNeil DE, Tagle D, Griebel DJ, Kaler SG, Mink JW, Shapiro EG, Bjoraker KJ, Krivitzky L, Provenzale JM, Gropman A, Orchard P, Raymond G, Cohen BH, Steiner RD, Goldkind SF, Nelson RM, Kakkis E, Patterson MC. Mol Genet Metab. 2011 Mar;102(3):326-38. doi: 10.1016/j.ymgme.2010.11.164. Epub 2010 Dec 2.

Vaccines are not associated with metabolic events in children with urea cycle disorders. Morgan TM, Schlegel C, Edwards KM, Welch-Burke T, Zhu Y, Sparks R, Summar M; Urea Cycle Disorders Consortium. Pediatrics. 2011 May;127(5):e1147-53. doi: 10.1542/peds.2010-1628. Epub 2011 Apr 11.

An exon 1 deletion in OTC identified using chromosomal microarray analyses in a mother and her two affected deceased newborns: implications for the prenatal diagnosis of ornithine transcarbamylase deficiency. Quintero-Rivera F,  Deignan J, Peredo J,  Grody W, Crandall B,  Sims M, Cederbaum S. Mol Genet Metab. 2010;101:413-416. PMID: 20817516, Full Text (with PubMed access).

Brain imaging in urea cycle disorders. Gropman A. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S20-30. doi: 10.1016/j.ymgme.2010.01.017. Epub 2010 Feb 13.

Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency. Gropman AL, Gertz B, Shattuck K, Kahn IL, Seltzer R, Krivitsky L, Van Meter J. AJNR Am J Neuroradiol. 2010 Oct;31(9):1719-23. doi: 10.3174/ajnr.A2122. Epub 2010 May 20.

Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Pediatr Neurol. 2010 Jan;42(1):49-52. doi: 10.1016/j.pediatrneurol.2009.07.017.

Early orthotopic liver transplantation in urea cycle defects: follow up of a developmental outcome study. Campeau PM, Pivalizza PJ, Miller G, McBride K, Karpen S, Goss J, Lee BH. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S84-7. doi: 10.1016/j.ymgme.2010.02.012. Epub 2010 Feb 19.

Epigenetics, copy number variation, and other molecular mechanisms underlying neurodevelopmental disabilities: new insights and diagnostic approaches. Gropman AL, Batshaw ML. J Dev Behav Pediatr. 2010 Sep;31(7):582-91. doi: 10.1097/DBP.0b013e3181ee384e.

Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium. Seminara J, Tuchman M, Krivitzky L, Krischer J, Lee HS, Lemons C, Baumgartner M, Cederbaum S, Diaz GA, Feigenbaum A, Gallagher RC, Harding CO, Kerr DS, Lanpher B, Lee B, Lichter-Konecki U, McCandless SE, Merritt JL, Oster-Granite ML, Seashore MR, Stricker T, Summar M, Waisbren S, Yudkoff M, Batshaw ML. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S97-105. doi: 10.1016/j.ymgme.2010.01.014. Epub 2010 Feb 10.

Guanidino compound levels in blood, cerebrospinal fluid, and postmortem brain material of patients with argininemia. Deignan JL, De Deyn PP, Cederbaum SD, Fuchshuber A, Roth B, Gsell W,  Marescau B. Mol Genet Metab. 2010;100 (suppl):S31-S36. PMID: 20176499, Full Text (with PubMed access).

Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination. Mehta N, Cunningham CK, Flynn P, Pepe J, Obaro S, Kapogiannis BG, Bethel J, Luzuriaga K; Adolescent Trials Network for HIV/AIDS Interventions. Vaccine. 2010 May 7;28(21):3672-8. doi: 10.1016/j.vaccine.2010.03.022. Epub 2010 Mar 28.

L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in oxygen-induced lung injury in newborn rats. Vadivel A, Aschner JL, Rey-Parra GJ, Magarik J, Zeng H, Summar M, Eaton F, Thébaud B. Pediatr Res. 2010 Dec;68(6):519-25. doi: 10.1203/PDR.0b013e3181f90278.

Measuring in vivo ureagenesis with stable isotopes. Yudkoff M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, Payan I, Tuchman M. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S37-41. doi: 10.1016/j.ymgme.2010.02.017. Epub 2010 Feb 26.

Milder clinical course of Type IV 3-methylglutaconic aciduria due to a novel mutation in TMEM70. *Shchelochkov OA, Li FY, Wang J, Zhan H, Towbin JA, Jefferies JL, Wong LJ, Scaglia F. Mol Genet Metab. 2010 OctNov;101(2-3):282-285. PMID: 20728387, Full Text (with PubMed access).

N-acetylglutamate synthase: structure, function and defects. Caldovic L, Ah Mew N, Shi D, Morizono H, Yudkoff M, Tuchman M. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S13-9. doi: 10.1016/j.ymgme.2010.02.018. Epub 2010 Feb 26.

N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Ah Mew N, McCarter R, Daikhin Y, Nissim I, Yudkoff M, Tuchman M. Pediatrics. 2010 Jul;126(1):e208-14. doi: 10.1542/peds.2010-0008. Epub 2010 Jun 21.

NeuroD6 genomic signature bridging neuronal differentiation to survival via the molecular chaperone network. Uittenbogaard M, Baxter KK, Chiaramello A. J Neurosci Res. 2010 Jan;88(1):33-54. doi: 10.1002/jnr.22182.

Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Lee B, Rhead W, Diaz GA, Scharschmidt BF, Mian A, Shchelochkov O, Marier JF, Beliveau M, Mauney J, Dickinson K, Martinez A, Gargosky S, Mokhtarani M, Berry SA. Mol Genet Metab. 2010 Jul;100(3):221-8. doi: 10.1016/j.ymgme.2010.03.014. Epub 2010 Mar 23.

Randomized trial to determine safety and immunogenicity of two strategies for hepatitis B vaccination in healthy urban adolescents in the United States. Cunningham CK, Rudy BJ, Xu J, Bethel J, Kapogiannis BG, Ahmad S, Wilson CM, Flynn PM; Adolescent Medicine Trials Network for HIV/AIDS Interventions. Pediatr Infect Dis J. 2010 Jun;29(6):530-4. doi: 10.1097/INF.0b013e3181d285c7.

An automated communication system in a contact registry for persons with rare diseases: scalable tools for identifying and recruiting clinical research participants. Richesson RL, Lee HS, Cuthbertson D, Lloyd J, Young K, Krischer JP. Contemp Clin Trials. 2009 Jan;30(1):55-62. doi: 10.1016/j.cct.2008.09.002. Epub 2008 Sep 7.

Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders. Yerys BE, Wallace GL, Sokoloff JL, Shook DA, James JD, Kenworthy L. Autism Res. 2009 Dec;2(6):322-33. doi: 10.1002/aur.103.

Clinical research for rare disease: opportunities, challenges, and solutions. Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA; Rare Diseases Clinical Research Network. Mol Genet Metab. 2009 Jan;96(1):20-6. doi: 10.1016/j.ymgme.2008.10.003. Epub 2008 Nov 13.

Effects of a single dose of N-carbamylglutamate on the rate of ureagenesis. Ah Mew N, Payan I, Daikhin Y, Nissim I, Nissim I, Tuchman M, Yudkoff M. Mol Genet Metab. 2009 Dec;98(4):325-30. doi: 10.1016/j.ymgme.2009.07.010. Epub 2009 Jul 14.

Expression profiling of inflammatory mediators in pediatric sinus mucosa. Wu X, Ghimbovschi S, Aujla PK, Rose MC, Peña MT. Arch Otolaryngol Head Neck Surg. 2009 Jan;135(1):65-72. doi: 10.1001/archoto.2008.505.

Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseases. Mitchell S, Ellingson C, Coyne T, Hall L, Neill M, Christian N, Higham C, Dobrowolski SF, Tuchman M, Summar M; Urea Cycle Disorder Consortium. Hum Mutat. 2009 Jan;30(1):56-60. doi: 10.1002/humu.20813.

High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide Array CGH. Shchelochkov OA, Li F, Geraghty MT, Gallagher RC, Van Hove JL, Lichter-Konecki U, Fernhoff PM, Copeland S, Reimschisel,T, Cederbaum S, Lee B, Chinault AC, Wong L. Mol Genet Metab. 2009;96: 97-105. PMID: 19138872, Full Text (with PubMed access).

Intellectual, adaptive, and behavioral functioning in children with urea cycle disorders. Krivitzky L, Babikian T, Lee HS, Thomas NH, Burk-Paull KL, Batshaw ML. Pediatr Res. 2009 Jul;66(1):96-101. doi: 10.1203/PDR.0b013e3181a27a16.

Ornithine transcarbamylase deficiency with persistent abnormality in cerebral glutamate metabolism in adults. Gropman AL, Sailasuta N, Harris KC, Abulseoud O, Ross BD. Radiology. 2009 Sep;252(3):833-41. doi: 10.1148/radiol.2523081878. Epub 2009 Jun 30.

Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis. Venkateswaran L, Scaglia F, McLin V, Hertel P, Shchelochkov OA, Karpen S, Mahoney D Jr, Yee DL. Pediatr Blood Cancer. 2009 Jul;53(1):100-2. doi: 10.1002/pbc.22016.

Profiling of oxidative stress in patients with inborn errors of metabolism. Mc Guire PJ, Parikh A, Diaz GA. Mol Genet Metab. 2009 Sep-Oct;98(1-2):173-180. PMID: 19604711, PMCID: PMC2915835.

Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues. Neill MA, Aschner J, Barr F, Summar ML. Mol Genet Metab. 2009 Jun;97(2):121-7. doi: 10.1016/j.ymgme.2009.02.009. Epub 2009 Mar 3.

Systemic hypertension in two patients with ASL deficiency: a result of nitric oxide deficiency?. Brunetti-Pierri N, Erez A, Shchelochkov O, Craigen W, Lee B. Mol Genet Metab. 2009 Sep-Oct;98(1-2):195-7. doi: 10.1016/j.ymgme.2009.06.006. Epub 2009 Jun 13.

1H MRS allows brain phenotype differentiation in sisters with late onset ornithine transcarbamylase deficiency (OTCD) and discordant clinical presentations. Gropman AL, Seltzer RR, Yudkoff M, Sawyer A, VanMeter J, Fricke ST. Mol Genet Metab. 2008 May;94(1):52-60. doi: 10.1016/j.ymgme.2007.12.008. Epub 2008 Feb 11.

1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency. Gropman AL, Fricke ST, Seltzer RR, Hailu A, Adeyemo A, Sawyer A, van Meter J, Gaillard WD, McCarter R, Tuchman M, Batshaw M; Urea Cycle Disorders Consortium. Mol Genet Metab. 2008 Sep-Oct;95(1-2):21-30. doi: 10.1016/j.ymgme.2008.06.003. Epub 2008 Jul 26.

3-isobutylmethylxanthine inhibits hepatic urea synthesis: protection by agmatine. Nissim I, Horyn O, Nissim I, Daikhin Y, Wehrli SL, Yudkoff M. J Biol Chem. 2008 May 30;283(22):15063-71. doi: 10.1074/jbc.M800163200. Epub 2008 Mar 28.

A ground truth based comparative study on clustering of gene expression data. Zhu Y, Wang Z, Miller DJ, Clarke R, Xuan J, Hoffman EP, Wang Y. Front Biosci. 2008 May 1;13:3839-49. doi: 10.2741/2972.

Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe. Sailasuta N, Robertson LW, Harris KC, Gropman AL, Allen PS, Ross BD. J Magn Reson. 2008 Dec;195(2):219-25. doi: 10.1016/j.jmr.2008.09.012. Epub 2008 Sep 17.

Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases. Deardorff MA, Gaddipati H, Kaplan P, Sanchez-Lara PA, Sondheimer N, Spinner NB, Hakonarson H, Ficicioglu C, Ganesh J, Markello T, Loechelt B, Zand DJ, Yudkoff M, Lichter-Konecki U. Mol Genet Metab. 2008 Aug;94(4):498-502. doi: 10.1016/j.ymgme.2008.04.011. Epub 2008 Jun 3.

Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Tuchman M, Lee B, Lichter-Konecki U, Summar ML, Yudkoff M, Cederbaum SD, Kerr DS, Diaz GA, Seashore MR, Lee HS, McCarter RJ, Krischer JP, Batshaw ML; Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research Network. Mol Genet Metab. 2008 Aug;94(4):397-402. doi: 10.1016/j.ymgme.2008.05.004. Epub 2008 Jun 17.

Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes. Summar ML, Dobbelaere D, Brusilow S, Lee B. Acta Paediatr. 2008 Oct;97(10):1420-5. doi: 10.1111/j.1651-2227.2008.00952.x. Epub 2008 Jul 17.

Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V. Glia. 2008 Mar;56(4):365-77. doi: 10.1002/glia.20624.

N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers. Tuchman M, Caldovic L, Daikhin Y, Horyn O, Nissim I, Nissim I, Korson M, Burton B, Yudkoff M. Pediatr Res. 2008 Aug;64(2):213-7. doi: 10.1203/PDR.0b013e318179454b.

Neurometabolic disorders: urea-cycle disorder, outcomes, development and treatment. *Gropman AL, Rigas A. Pediatric Health. 2008;2(6):701-713. Full Text.

Phenotypic correction of ornithine transcarbamylase deficiency using low dose helper-dependent adenoviral vectors. Brunetti-Pierri N, Clarke C, Mane V, Palmer DJ, Lanpher B, Sun Q, O'Brien W, Lee B. J Gene Med. 2008 Aug;10(8):890-896. PMID: 18563850, PMCID: PMC2766563.

Profiling of astrocyte properties in the hyperammonaemic brain: shedding new light on the pathophysiology of the brain damage in hyperammonaemia. Lichter-Konecki U. J Inherit Metab Dis. 2008 Aug;31(4):492-502. doi: 10.1007/s10545-008-0834-9. Epub 2008 Aug 9.

Recommendations for locusspecific databases and their curation. Cotton RG, Auerbach AD, Beckmann JS, Blumenfeld OO, Brookes AJ, Brown AF, Carrera P, Cox DW, Gottlieb B, Greenblatt MS, Hilbert P, Lehvaslaiho H, Liang P, Marsh S, Nebert DW, Povey S, Rossetti S, Scriver CR, Summar M, Tolan DR, Verma IC, Vihinen M, den Dunnen JT. Hum Mutat. 2008;29(1):2-5. PMID: 18157828, PMCID: PMC2752432.

SNOMED CT coding variation and grouping for "other findings" in a longitudinal study on urea cycle disorders. Patrick TB, Richesson R, Andrews JE, Folk LC. AMIA Annu Symp Proc. 2008 Nov 6;2008:11-5.

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia. Dimmock DP, Trapane P, Feigenbaum A, Keegan CE, Thoene J, Cederbaum S, Gibson J, Gambello M, Muenzer J, Vaux K, O'Brien WO, Fang P. Dimmock DP, Trapane P, Feigenbaum A, Keegan CE, Thoene J, Cederbaum S, Gibson J, Gambello M, Muenzer J, Vaux K, O'Brien WO, Fang P. The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia. Am J Med Genet A. 2008 Nov 15; 146A(22): 2885–2890. PMID: 18925679, PMCID: PMC2597641

Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs. Eeds AM, Mortlock D, Wade-Martins R, Summar ML. Am J Hum Genet. 2007 Apr;80(4):740-50. doi: 10.1086/513287. Epub 2007 Mar 8.

Citrin deficiency: A novel cause of failure to thrive that responds to a high protein, low carbohydrate diet. Dimmock DP, Kobayashi K, Iijima M, Tabata A, Wong LJ, Lee B, Saheki T, Scaglia F. Pediatrics. 2007;119:e773-e777. PMID: 17332192, Full Text (with PubMed access).

Mutations and polymorphisms in the human N-acetylglutamate synthase gene. Caldovic L, Morizono H, Tuchman M. Hum Mutat. 2007;28:754-759. PMID: 17421020, Full Text.

Neurological implications of urea cycle disorders. Gropman AL, Summar M, Leonard JV. J Inherit Metab Dis. 2007 Nov;30(6):865-79. doi: 10.1007/s10545-007-0709-5. Epub 2007 Nov 23.

Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine. *Marini JC, Lanpher B, Scaglia F, Carter S, Garlick PJ, Jahoor F, Lee B. FASEB Journal. 2007;21:A335. Abstract.

Role of branched chain amino acids in patients with urea cycle disorders. *Scaglia F, Lanpher B, Marini J, Lee B. In: Bachmann C, Haberle J, Leonard JV (eds). Pathophysiology and Management of Hyperammonemia. SPS Publications, 2007: p.65-75. 

Streamlined assessment of gene variants by high resolution melt profiling utilizing the ornithine transcarbamylase gene as a model system. Dobrowolski SF, Ellingson C, Caldovic L, Tuchman M. Hum Mutat. 2007;28:1133-1140. PMID: 17565723.

The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. Annu Rev Nutr. 2007;27:415-30. doi: 10.1146/annurev.nutr.27.061406.093722.

Urea cycle disorders. *EA Crombez, SD Cederbaum. In: Schapira AHV (ed) Neurology and Clinical Neuroscience. Mosby 2007, chapter 110, pp1469-1476.

Clinical and functional characterization of a human ORNT1mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Camacho JA, Mardach MR, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD. Pediatr Res. 2006;60:423-429. PMID: 16940241, Full Text.

Inborn errors of metabolism: the flux from Mendelian to complex diseases. Lanpher B, Brunetti-Pierri N, Lee B. Nat Rev Genet. 2006 Jun;7(6):449-60. doi: 10.1038/nrg1880.

Mutations and polymorphisms in the human ornithine transcarbamylase gene. Yamaguchi S, Brailey LL, Morizono H, Lynch MG, Bale AE, Tuchman M. Hum Mutat. 2006;27:626-632. PMID: 11793468, Full Text.

The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency. Eeds AM, Hall LD, Yadav M, Willis A, Summar S, Putnam A, Barr F, Summar ML. Mol Genet Metab. 2006 Sep-Oct;89(1-2):80-6. doi: 10.1016/j.ymgme.2006.04.006. Epub 2006 Jun 5.

Considerations in the difficult-to-manage urea cycle disorder patient. Lee B, Singh RH, Rhead WJ, Sniderman King L, Smith W, Summar ML. Crit Care Clin. 2005 Oct;21(4 Suppl):S19-25. doi: 10.1016/j.ccc.2005.05.001.

Genetic counseling issues in urea cycle disorders. Sniderman King L, Singh RH, Rhead WJ, Smith W, Lee B, Summar ML. Crit Care Clin. 2005 Oct;21(4 Suppl):S37-44. doi: 10.1016/j.ccc.2005.08.001.

Hyperargininemia due to liver arginase deficiency. Crombez EA, Cederbaum SD. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. Epub 2004 Dec 19.

Management and outcome of neonatal-onset ornithine transcarbamylase deficiency following liver transplantation at 60 days of life. Ensenauer R, Tuchman M, El-Youssef M, Kotagal S, Ishitani MB, Matern D, Babovic-Vuksanovic D. Mol Genet Metab. 2005;84:363-366 PMID: 15781198, Full Text (with PubMed access).

Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Kallianpur AR, Summar M, Canter JA. AIDS. 2005 Sep 2;19(13):1341-9. doi: 10.1097/01.aids.0000180786.02930.a1.

Nutritional management of urea cycle disorders. Singh RH, Rhead WJ, Smith W, Lee B, Sniderman King L, Summar M. Crit Care Clin. 2005 Oct;21(4 Suppl):S27-35. doi: 10.1016/j.ccc.2005.08.003.

Unmasked adult-onset urea cycle disorders in the critical care setting. Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Crit Care Clin. 2005 Oct;21(4 Suppl):S1-8. doi: 10.1016/j.ccc.2005.05.002.

Urea cycle disorders: clinical presentation outside the newborn period. Smith W, Kishnani PS, Lee B, Singh RH, Rhead WJ, Sniderman King L, Smith M, Summar M. Crit Care Clin. 2005 Oct;21(4 Suppl):S9-17. doi: 10.1016/j.ccc.2005.05.007.

Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, O'Brien W, Lee B. J Nutr. 2004 Oct;134(10 Suppl):2775S-2782S; discussion 2796S-2797S. doi: 10.1093/jn/134.10.2775S.

Cognitive outcome in urea cycle disorders. Gropman AL, Batshaw ML. Mol Genet Metab. 2004 Apr;81 Suppl 1:S58-62. doi: 10.1016/j.ymgme.2003.11.016.

Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Scaglia F, Carter S, O’Brien W, Lee B. Mol Genet Metab. 2004;81S:79-85. PMID: 15050979, Full Text (with PubMed access).

Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Summar ML, Hall LD, Christman B, Barr F, Smith H, Kallianpur A, Brown N, Yadav M, Willis A, Eeds A, Cermak E, Summar S, Wilson A, Arvin M, Putnam A, Wills M, Cunningham G. Mol Genet Metab. 2004;81(Suppl 1):S12-S19. PMID: 15050969, Full Text (with PubMed access).

Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man and family studies. Rohininath T, Costello DJ, Lynch T, Monavari A, Tuchman M, Treacy EP. J Inherit Metab Dis. 2004;27:285-288. PMID: 15243986.

Hyperammonemia: are the burdens too grave? Case study. Tuchman M. Ethics Intellect Disabil. 2004;8:1,3. PMID: 15835081.

Long-term correction of ornithine transcarbamylase deficiency by WPRE-mediated overexpression using a helper-dependent adenovirus. Mian A, McCormack WM Jr, Mane V, Kleppe S, Ng P, Finegold M, O'Brien WE, Rodgers JR, Beaudet AL, Lee B. Mol Ther. 2004 Sep;10(3):492-9. doi: 10.1016/j.ymthe.2004.05.036.

New secondary metabolites of phenylbutyrate in humans and rats. Kasumov T, Brunengraber LL, Comte B, Puchowicz MA, Jobbins K, Thomas K, David F, Kinman R, Wehrli S, Dahms W, Kerr D, Nissim I, Brunengraber H. Drug Metab Dispos. 2004;32:10-19. PMID: 14709615, Full Text.

Pharmacokinetics of sodium phenylacetate and sodium benzoate following intravenous administration as both a bolus and continuous infusion to healthy adult volunteers. MacArthur RB, Altincatal A, Tuchman M. Mol Genet Metab. 2004;Suppl:67-73. PMID: 15050977, Full Text (with PubMed access).

Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M. J Pediatr. 2004 Oct;145(4):552-4. doi: 10.1016/j.jpeds.2004.06.047.

Urea cycle disorders workshop introduction. Tuchman M. Mol Genet Metab. 2004;81(Suppl):3. Full Text.

Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders. Takanashi JI, Barkovich AJ, Cheng SF, Weisiger K, Zlatunich CO, Mudge C, Rosenthal P, Tuchman M, Packman S. Am J Neuroradiol. 2003;24:1184-1187. PMID: 12812952, Full Text.

Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene. Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, Rubio V, Arvin MK, Schofield JP, Dawson EP. Gene. 2003;311:51-57. PMID: 12853138, Full Text (with PubMed access).

Differential utilization of systemic and enteral ammonia for urea synthesis in control subjects and carriers for ornithine transcarbamylase deficiency. Scaglia F, Rosenberger J, Henry J, Lee B, Reeds P. Am J Clin Nutr. 2003;78:749-755. PMID: 14522733, Full Text.

Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery. Barr FE, Beverley H, VanHook K, Cermak E, Christian K, Drinkwater D, Dyer K, Raggio NT, Moore JH, Christman B, Summar M. J Pediatr. 2003;142(1):26-30. PMID: 12520250, Full Text (with PubMed access).

Null mutations in the Nacetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Caldovic L, Morizono M, Panglao M, Cheng SF, Packman S, Tuchman M. Hum Genet. 2003;112:364-368. PMID: 12594532, Full Text (with PubMed access).

Urea Cycle Disorders. Kleppe S, Mian A, Lee B. Curr Treat Options Neurol. 2003 Jul;5(4):309-319. doi: 10.1007/s11940-003-0037-5.

Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study. Applequist J, Burroughs C, Merkel PA, Rothenberg M, Trapnell B, Desnick R, Sahin M, Krischer J. J Med Internet Res. 2023 Mar 14;25:e39262. doi: 10.2196/39262.

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing. Ortiz-Fernández L, Carmona EG, Kerick M, Lyons P, Carmona FD, López Mejías R, Khor CC, Grayson PC, Tombetti E, Jiang L, Direskeneli H, Saruhan-Direskeneli G, Callejas-Rubio JL, Vaglio A, Salvarani C, Hernández-Rodríguez J, Cid MC, Morgan AW, Merkel PA, Burgner D, Smith KG, Gonzalez-Gay MA, Sawalha AH, Martin J, Marquez A. Ann Rheum Dis. 2023 Jun;82(6):837-847. doi: 10.1136/ard-2022-223697. Epub 2023 Feb 16.

Mitochondrial-mediated inflammation and platelet activation in giant cell arteritis. Michailidou D, Grayson PC, Hermanson P, Chapa JAG, Cuthbertson D, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Pagnoux C, Seo P, Sreih AG, Warrington KJ, Monach PA, Merkel PA, Lood C. Clin Immunol. 2023 Oct;255:109746. doi: 10.1016/j.clim.2023.109746. Epub 2023 Aug 23.

Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis. Michailidou D, Kuley R, Wang T, Hermanson P, Grayson PC, Cuthbertson D, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Warrington KJ, Monach PA, Merkel PA, Lood C. Clin Immunol. 2023 Apr;249:109274. doi: 10.1016/j.clim.2023.109274. Epub 2023 Mar 4.

Ocular manifestations of ANCA-associated vasculitis. Junek ML, Zhao L, Garner S, Cuthbertson D, Pagnoux C, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Rhee RL, Seo P, Specks U, Sreih AG, Warrington K, Wechsler ME, Merkel PA, Khalidi NA. Rheumatology (Oxford). 2023 Jul 5;62(7):2517-2524. doi: 10.1093/rheumatology/keac663.

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Smith RM, Jones RB, Specks U, Bond S, Nodale M, Al-Jayyousi R, Andrews J, Bruchfeld A, Camilleri B, Carette S, Cheung CK, Derebail V, Doulton T, Ferraro A, Forbess L, Fujimoto S, Furuta S, Gewurz-Singer O, Harper L, Ito-Ihara T, Khalidi N, Klocke R, Koening C, Komagata Y, Langford C, Lanyon P, Luqmani R, McAlear C, Moreland LW, Mynard K, Nachman P, Pagnoux C, Peh CA, Pusey C, Ranganathan D, Rhee RL, Spiera R, Sreih AG, Tesar V, Walters G, Wroe C, Jayne D, Merkel PA; RITAZAREM co-investigators.. Ann Rheum Dis. 2023 Jul;82(7):937-944. doi: 10.1136/ard-2022-223559. Epub 2023 Mar 23.

The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With ANCA-Associated Vasculitis. Bloom JL, Pickett-Nairn K, Silveira L, Fuhlbrigge RC, Cuthbertson D, Akuthota P, Corbridge TC, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Rhee RL, Seo P, Silver J, Specks U, Warrington KJ, Wechsler ME, Merkel PA; Vasculitis Clinical Research Consortium. Arthritis Rheumatol. 2023 Dec;75(12):2216-2227. doi: 10.1002/art.42651. Epub 2023 Oct 5.

Vitamin D status in ANCA-associated vasculitis. Doubelt I, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford C, McAlear CA, Moreland LW, Monach P, Seo P, Specks U, Warrington KJ, Merkel PA, Pagnoux C. Rheumatol Adv Pract. 2023 Feb 10;7(1):rkad021. doi: 10.1093/rap/rkad021. eCollection 2023.PMID: 36874269.

Core Set of Domains for Outcome Measures in Behçet's Syndrome. Hatemi G, Meara A, Özgüler Y, Direskeneli H, Mahr A, Shea B, Cam E, Gul A, Yazici Y, Tugwell P, Yazici H, Merkel PA; Outcome Measures in Rheumatology Behçet's Syndrome Working Group. Arthritis Care Res (Hoboken). 2022 Apr;74(4):691-699. doi: 10.1002/acr.24511. Epub 2022 Mar 4.

Hypothyroidism in vasculitis. Kermani TA, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland L, Pagnoux C, Seo P, Specks U, Sreih A, Warrington KJ, Merkel PA; Vasculitis Clinical Research Consortium. Rheumatology (Oxford). 2022 Jul 6;61(7):2942-2950. doi: 10.1093/rheumatology/keab817.

Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis. Michailidou D, Duvvuri B, Kuley R, Cuthbertson D, Grayson PC, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Warrington KJ, Mustelin T, Monach PA, Merkel PA, Lood C.. Arthritis Res Ther. 2022 Jun 29;24(1):160. doi: 10.1186/s13075-022-02849-z.

Self-Reported Data and Physician-Reported Data in Patients With Eosinophilic Granulomatosis With Polyangiitis: Comparative Analysis. Doubelt I, Springer JM, Kermani TA, Sreih AG, Burroughs C, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford C, McAlear CA, Moreland LW, Monach PA, Shaw DG, Seo P, Specks U, Warrington KJ, Young K, Merkel PA, Pagnoux C. Interact J Med Res. 2022 May 25;11(1):e27273. doi: 10.2196/27273.PMID: 35612893.

Clinical Manifestations and Long-Term Outcomes of Eosinophilic Granulomatosis With Polyangiitis in North America. Doubelt I, Cuthbertson D, Carette S, Chung SA, Forbess LJ, Khalidi NA, Koening CL, Langford C, McAlear CA, Moreland LW, Monach PA, Seo P, Specks U, Spiera RF, Springer JM, Sreih AG, Warrington KJ, Merkel PA, Pagnoux C; Vasculitis Clinical Research Consortium. ACR Open Rheumatol. 2021 May 25. doi: 10.1002/acr2.11263. Online ahead of print.

Clinical pathways for patients with giant cell arteritis during the COVID-19 pandemic: an international perspective. Mackie SL, Brouwer E, Conway R, van der Geest KSM, Mehta P, Mollan SP, Neill L, Putman M, Robinson PC, Sattui SE. Lancet Rheumatol. 2021 Jan;3(1):e71-e82. doi: 10.1016/S2665-9913(20)30386-6. Epub 2020 Dec 8.

Diagnostic delays in vasculitis and factors associated with time to diagnosis. Sreih AG, Cronin K, Shaw DG, Young K, Burroughs C, Kullman J, Machireddy K, McAlear CA, Merkel PA; Vasculitis Patient-Powered Research Network. Orphanet J Rare Dis. 2021 Apr 21;16(1):184. doi: 10.1186/s13023-021-01794-5.

Efficacy of leflunomide in the treatment of vasculitis. Mustapha N, Barra L, Carette S, Cuthbertson D, Khalidi NA, Koening CL, Langford CA, McAlear CA, Milman N, Moreland LW, Monach PA, Seo P, Specks U, Sreih AG, Ytterberg SY, Merkel PA, Pagnoux C; Canadian Vasculitis Research Network (CanVasc) and Vasculitis Clinical Research Consortium (VCRC). Clin Exp Rheumatol. 2021 Mar-Apr;39 Suppl 129(2):114-118. doi: 10.55563/clinexprheumatol/ve38dj. Epub 2020 Nov 10.PMID: 33200732.

Giant Cell Arteritis and COVID-19: Similarities and Discriminators. A Systematic Literature Review. Mehta P, Sattui SE, van der Geest KSM, Brouwer E, Conway R, Putman MS, Robinson PC, Mackie SL. J Rheumatol. 2021 Jul;48(7):1053-1059. doi: 10.3899/jrheum.200766. Epub 2020 Oct 15.

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study. Ortiz-Fernández L, Saruhan-Direskeneli G, Alibaz-Oner F, Kaymaz-Tahra S, Coit P, Kong X, Kiprianos AP, Maughan RT, Aydin SZ, Aksu K, Keser G, Kamali S, Inanc M, Springer J, Akar S, Onen F, Akkoc N, Khalidi NA, Koening C, Karadag O, Kiraz S, Forbess L, Langford CA, McAlear CA, Ozbalkan Z, Yavuz S, Çetin GY, Alpay-Kanitez N, Chung S, Ates A, Karaaslan Y, McKinnon-Maksimowicz K, Monach PA, Ozer HTE, Seyahi E, Fresko I, Cefle A, Seo P, Warrington KJ, Ozturk MA, Ytterberg SR, Cobankara V, Onat AM, Duzgun N, Bıcakcıgil M, Yentür SP, Lally L, Manfredi AA, Baldissera E, Erken E, Yazici A, Kısacık B, Kaşifoğlu T, Dalkilic E, Cuthbertson D, Pagnoux C, Sreih A, Reales G, Wallace C, Wren JD, Cunninghame-Graham DS, Vyse TJ, Sun Y, Chen H, Grayson PC, Tombetti E, Jiang L, Mason JC, Merkel PA, Direskeneli H, Sawalha AH. Am J Hum Genet. 2021 Jan 7;108(1):84-99. doi: 10.1016/j.ajhg.2020.11.014. Epub 2020 Dec 11.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study. Sattui SE, Conway R, Putman MS, Seet AM, Gianfrancesco MA, Beins K, Hill C, Liew D, Mackie SL, Mehta P, Neill L, Gomez G, Salinas MIH, Maldonado FN, Mariz HA, de Sousa Studart SA, Araujo NC, Knight A, Rozza D, Quartuccio L, Samson M, Bally S, Maria AT, Chazerain P, Hasseli R, Müller-Ladner U, Hoyer BF, Voll R, Torres RP, Luis M, Ribeirio SLE, Al-Emadi S, Sparks JA, Hsu TY, D'Silva KM, Patel NJ, Wise L, Gilbert E, Almada MV, Duarte-García A, Ugarte-Gil M, Jacobsohn L, Izadi Z, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, Carmona L, Lawson-Tovey S, Kearsley-Fleet L, Schaefer M, Sirotich E, Hausmann JS, Sufka P, Bhana S, Liew JW, Grainger R, Machado PM, Wallace ZS, Yazdany J, Robinson PC; Global Rheumatology Alliance. Lancet Rheumatol. 2021 Dec;3(12):e855-e864. doi: 10.1016/S2665-9913(21)00316-7. Epub 2021 Nov 5.

Reconsidering 'minimal risk' to expand the repertoire of trials with waiver of informed consent for research. Monach PA, Branch-Elliman W. BMJ Open. 2021 Sep 14;11(9):e048534. doi: 10.1136/bmjopen-2020-048534.

Sequence-Based Screening of Patients With Idiopathic Polyarteritis Nodosa, Granulomatosis With Polyangiitis, and Microscopic Polyangiitis for Deleterious Genetic Variants in ADA2. Schnappauf O, Sampaio Moura N, Aksentijevich I, Stoffels M, Ombrello AK, Hoffmann P, Barron K, Remmers EF, Hershfield M, Kelly SJ; NISC Comparative Sequencing Program; Cuthbertson D, Carette S, Chung SA, Forbess L, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland L, Pagnoux C, Seo P, Springer JM, Sreih AG, Warrington KJ, Ytterberg SR, Kastner DL, Grayson PC, Merkel PA; Vasculitis Clinical Research Consortium. Arthritis Rheumatol. 2021 Mar;73(3):512-519. doi: 10.1002/art.41549. Epub 2021 Feb 3.PMID: 33021335.

Serum Biomarkers of Disease Activity in Longitudinal Assessment of Patients with ANCA-Associated Vasculitis. Monach PA, Warner RL, Lew R, Tómasson G, Specks U, Stone JH, Fervenza FC, Hoffman GS, Kallenberg CGM, Langford CA, Seo P, St Clair EW, Spiera R, Johnson KJ, Merkel PA. ACR Open Rheumatol. 2021 Nov 18. doi: 10.1002/acr2.11366. Online ahead of print.

The Immunopathology of Giant Cell Arteritis Across Disease Spectra. Robinette ML, Rao DA, Monach PA. Front Immunol. 2021 Feb 25;12:623716. doi: 10.3389/fimmu.2021.623716. eCollection 2021.

A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.

Clinical Characteristics of an Internet-Based Cohort of Patient-Reported Diagnosis of Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Observational Study. Springer JM, Kermani TA, Sreih A, Shaw DG, Young K, Burroughs CM, Merkel PA. J Med Internet Res. 2020 Jul 20;22(7):e17231. doi: 10.2196/17231.

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America. Goel R, Gribbons KB, Carette S, Cuthbertson D, Hoffman GS, Joseph G, Khalidi NA, Koening CL, Kumar S, Langford C, Maksimowicz-McKinnon K, McAlear CA, Monach PA, Moreland LW, Nair A, Pagnoux C, Quinn KA, Ravindran R, Seo P, Sreih AG, Warrington KJ, Ytterberg SR, Merkel PA, Danda D, Grayson PC. Rheumatology (Oxford). 2020 May 1;59(5):1118-1127. doi: 10.1093/rheumatology/kez421.

Effect of Treatment on Imaging, Clinical, and Serologic Assessments of Disease Activity in Large-vessel Vasculitis. Banerjee S, Quinn KA, Gribbons KB, Rosenblum JS, Civelek AC, Novakovich E, Merkel PA, Ahlman MA, Grayson PC. J Rheumatol. 2020 Jan;47(1):99-107. doi: 10.3899/jrheum.181222. Epub 2019 Mar 15.

Evaluation of Potential Serum Biomarkers of Disease Activity in Diverse Forms of Vasculitis. Rodriguez-Pla A, Warner RL, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Johnson KJ, Merkel PA, Monach PA; Vasculitis Clinical Research Consortium. J Rheumatol. 2020 Jul 1;47(7):1001-1010. doi: 10.3899/jrheum.190093. Epub 2019 Sep 1.

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis. Quinn KA, Rosenblum JS, Rimland CA, Gribbons KB, Ahlman MA, Grayson PC. Semin Arthritis Rheum. 2020 Feb;50(1):71-76. doi: 10.1016/j.semarthrit.2019.07.008. Epub 2019 Jul 24.

Patterns of Arterial Disease in Takayasu Arteritis and Giant Cell Arteritis. Gribbons KB, Ponte C, Carette S, Craven A, Cuthbertson D, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Quinn KA, Robson JC, Seo P, Sreih AG, Suppiah R, Warrington KJ, Ytterberg SR, Luqmani R, Watts R, Merkel PA, Grayson PC. Arthritis Care Res (Hoboken). 2020 Nov;72(11):1615-1624. doi: 10.1002/acr.24055.

Patterns of clinical presentation in Takayasu's arteritis. Quinn KA, Gribbons KB, Carette S, Cuthbertson D, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Seo P, Sreih AG, Warrington KJ, Ytterberg SR, Novakovich E, Merkel PA, Grayson PC. Semin Arthritis Rheum. 2020 Aug;50(4):576-581. doi: 10.1016/j.semarthrit.2020.04.012. Epub 2020 May 19.

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, Hawley CM, Khalidi N, Floßmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suárez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators. N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. Reply. Walsh M, Merkel PA, Jayne DRW. N Engl J Med. 2020 May 28;382(22):2169. doi: 10.1056/NEJMc2004843.

Protocol for a randomized multicenter study for isolated skin vasculitis (ARAMIS) comparing the efficacy of three drugs: azathioprine, colchicine, and dapsone. Micheletti RG, Pagnoux C, Tamura RN, Grayson PC, McAlear CA, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. Trials. 2020 Apr 28;21(1):362. doi: 10.1186/s13063-020-04285-3.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Smith RM, Jones RB, Specks U, Bond S, Nodale M, Aljayyousi R, Andrews J, Bruchfeld A, Camilleri B, Carette S, Cheung CK, Derebail V, Doulton T, Forbess L, Fujimoto S, Furuta S, Gewurz-Singer O, Harper L, Ito-Ihara T, Khalidi N, Klocke R, Koening C, Komagata Y, Langford C, Lanyon P, Luqmani RA, Makino H, McAlear CA, Monach P, Moreland LW, Mynard K, Nachman P, Pagnoux C, Pearce F, Peh CA, Pusey C, Ranganathan D, Rhee RL, Spiera R, Sreih AG, Tesar V, Walters G, Weisman MH, Wroe C, Merkel PA, Jayne D; RITAZAREM coinvestigators; RITAZAREM co-investigators. Ann Rheum Dis. 2020 Sep;79(9):1243-1249. doi: 10.1136/annrheumdis-2019-216863. Epub 2020 Jun 24.PMID: 32581088.

Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Moran SM, Monach PA, Zgaga L, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland L, Pagnoux C, Seo P, Specks U, Sreih A, Wyse J, Ytterberg SR, Merkel PA, Little MA; Vasculitis Clinical Research Consortium. Nephrol Dial Transplant. 2020 Feb 1;35(2):283-291. doi: 10.1093/ndt/gfy300.

Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID-19: A Case Series. Navarro-Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH, Crow MK. Arthritis Rheumatol. 2020 Dec;72(12):1990-1997. doi: 10.1002/art.41422. Epub 2020 Nov 4.

Arterial lesions in giant cell arteritis: A longitudinal study. Kermani TA, Diab S, Sreih AG, Cuthbertson D, Borchin R, Carette S, Forbess L, Koening CL, McAlear CA, Monach PA, Moreland L, Pagnoux C, Seo P, Spiera RF, Warrington KJ, Ytterberg SR, Langford CA, Merkel PA, Khalidi NA; Vasculitis Clinical Research Consortium. Semin Arthritis Rheum. 2019 Feb;48(4):707-713. doi: 10.1016/j.semarthrit.2018.05.002. Epub 2018 May 9.

Disease Activity, Antineutrophil Cytoplasmic Antibody Type, and Lipid Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Wallace ZS, Fu X, Liao K, Kallenberg CGM, Langford CA, Merkel PA, Monach P, Seo P, Specks U, Spiera R, St Clair EW, Zhang Y, Choi H, Stone JH. Arthritis Rheumatol. 2019 Nov;71(11):1879-1887. doi: 10.1002/art.41006. Epub 2019 Sep 16.

Feasibility and Construct Validation of the Patient Reported Outcomes Measurement Information System in Systemic Vasculitis. Tomasson G, Farrar JT, Cuthbertson D, McAlear CA, Ashdown S, Cronholm PF, Dawson J, Gebhart D, Lanier G, Luqmani RA, Milman N, Peck J, Robson JC, Shea JA, Carette S, Khalidi N, Koening CL, Langford CA, Monach PA, Moreland L, Pagnoux C, Specks U, Sreih AG, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. J Rheumatol. 2019 Aug;46(8):928-934. doi: 10.3899/jrheum.171405. Epub 2019 Mar 1.

Genetic Variants in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Bayesian Approach and Systematic Review. Lee KS, Kronbichler A, Pereira Vasconcelos DF, Pereira da Silva FR, Ko Y, Oh YS, Eisenhut M, Merkel PA, Jayne D, Amos CI, Siminovitch KA, Rahmattulla C, Lee KH, Shin JI. J Clin Med. 2019 Feb 21;8(2):266. doi: 10.3390/jcm8020266.

MultiPLIER: A Transfer Learning Framework for Transcriptomics Reveals Systemic Features of Rare Disease. Taroni JN, Grayson PC, Hu Q, Eddy S, Kretzler M, Merkel PA, Greene CS. Cell Syst. 2019 May 22;8(5):380-394.e4. doi: 10.1016/j.cels.2019.04.003.

Patient involvement in medical research: what patients and physicians learn from each other. Young K, Kaminstein D, Olivos A, Burroughs C, Castillo-Lee C, Kullman J, McAlear C, Shaw DG, Sreih A, Casey G; Vasculitis Patient-Powered Research Network, Merkel PA. Orphanet J Rare Dis. 2019 Jan 24;14(1):21. doi: 10.1186/s13023-018-0969-1.

Patients' experiences with Behçet's syndrome: structured interviews among patients with different types of organ involvement. Ozguler Y, Merkel PA, Gurcan M, Bocage C, Eriksen W, Kutlubay Z, Hatemi G, Cronholm PF; OMERACT Behçet's Syndrome Working Group. Clin Exp Rheumatol. 2019 Nov-Dec;37 Suppl 121(6):28-34. Epub 2019 Apr 12.

Serum cytokine and chemokine levels in patients with eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, or eosinophilic asthma. Pagnoux C, Nair P, Xi Y, Khalidi NA, Carette S, Cuthbertson D, Grayson PC, Koening CL, Langford CA, McAlear CA, Moreland LW, Monach PA, Seo P, Specks U, Sreih AG, Ytterberg SR, Tyrrell PN, Merkel PA; Vasculitis Clinical Research Consortium. Clin Exp Rheumatol. 2019 Mar-Apr;37 Suppl 117(2):40-44. Epub 2019 Jan 14.

Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Quinn KA, Gelbard A, Sibley C, Sirajuddin A, Ferrada MA, Chen M, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Merkel PA, Grayson PC. Rheumatology (Oxford). 2019 Dec 1;58(12):2203-2211. doi: 10.1093/rheumatology/kez217.

The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis. Berti A, Warner R, Johnson K, Cornec D, Schroeder DR, Kabat BF, Langford CA, Kallenberg CGM, Seo P, Spiera RF, St Clair EW, Fervenza FC, Stone JH, Monach PA, Specks U, Merkel PA; RAVE-ITN Research Group. J Autoimmun. 2019 Dec;105:102302. doi: 10.1016/j.jaut.2019.07.001. Epub 2019 Jul 15.

Update on Outcome Measure Development in Large-vessel Vasculitis: Report from OMERACT 2018. Aydin SZ, Robson JC, Sreih AG, Hill C, Alibaz-Oner F, Mackie S, Beard S, Gul A, Hatemi G, Kermani TA, Mahr A, Meara A, Milman N, Shea B, Tómasson G, Tugwell P, Direskeneli H, Merkel PA. J Rheumatol. 2019 Sep;46(9):1198-1201. doi: 10.3899/jrheum.181072. Epub 2019 Mar 15.

Updating OMERACT Core Set of Domains for ANCA-associated Vasculitis: Patient Perspective Using the International Classification of Function, Disability, and Health. Milman N, McConville E, Robson JC, Boonen A, Tugwell P, Wells GA, Chaudhuri D, Dawson J, Tomasson G, Ashdown S, Gebhart D, Lanier G, Peck J, McAlear CA, Kellom KS, Cronholm PF, Merkel PA. J Rheumatol. 2019 Oct;46(10):1415-1420. doi: 10.3899/jrheum.181073. Epub 2019 Feb 1.

(18) F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis. Grayson PC, Alehashemi S, Bagheri AA, Civelek AC, Cupps TR, Kaplan MJ, Malayeri AA, Merkel PA, Novakovich E, Bluemke DA, Ahlman MA. Arthritis Rheumatol. 2018 Mar;70(3):439-449. doi: 10.1002/art.40379. Epub 2018 Feb 6.

Brief Report: Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B, Langford CA, Hoffman GS, Fervenza FC, Kallenberg CGM, Seo P, Spiera R, St Clair EW, Brunetta P, Stone JH, Merkel PA, Specks U, Monach PA; RAVE-ITN Research Group. Arthritis Rheumatol. 2018 Jul;70(7):1114-1121. doi: 10.1002/art.40471. Epub 2018 May 7.

CNS Vasculitis: an Approach to Differential Diagnosis and Management. Byram K, Hajj-Ali RA, Calabrese L. Curr Rheumatol Rep. 2018 May 30;20(7):37. doi: 10.1007/s11926-018-0747-z.

Comparison of magnetic resonance angiography and (18)F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Quinn KA, Ahlman MA, Malayeri AA, Marko J, Civelek AC, Rosenblum JS, Bagheri AA, Merkel PA, Novakovich E, Grayson PC. Ann Rheum Dis. 2018 Aug;77(8):1165-1171. doi: 10.1136/annrheumdis-2018-213102. Epub 2018 Apr 17.

Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus for the development of systemic vasculitis. Ortiz-Fernández L, Carmona FD, López-Mejías R, González-Escribano MF, Lyons PA, Morgan AW, Sawalha AH, Merkel PA, Smith KGC, González-Gay MA, Martín J; Spanish GCA Study Group, UK GCA Consortium, Turkish Takayasu Study Group, Vasculitis Clinical Research Consortium, IgAV Study Group, AAV Study group. Ann Rheum Dis. 2018 Apr;77(4):589-595. doi: 10.1136/annrheumdis-2017-212372. Epub 2018 Jan 27.

Evaluation of damage in giant cell arteritis. Kermani TA, Sreih AG, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland L, Pagnoux C, Seo P, Warrington KJ, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. Rheumatology (Oxford). 2018 Feb 1;57(2):322-328. doi: 10.1093/rheumatology/kex397.

Health-related quality of life in ANCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure. Robson JC, Dawson J, Cronholm PF, Milman N, Kellom KS, Ashdown S, Easley E, Farrar JT, Gebhart D, Lanier G, McAlear CA, Peck J, Luqmani RA, Shea JA, Tomasson G, Merkel PA. Patient Relat Outcome Meas. 2018 Jan 4;9:17-34. doi: 10.2147/PROM.S144992. eCollection 2018.

Impact of vasculitis on employment and income. Barra L, Borchin RL, Burroughs C, Casey GC, McAlear CA, Sreih AG, Young K, Merkel PA, Pagnoux C; Vasculitis Clinical Research Consortium and the Vasculitis Patient-Powered Research Network. Clin Exp Rheumatol. 2018 Mar-Apr;36 Suppl 111(2):58-64. Epub 2018 Jan 10.

Metabolic pathways and immunometabolism in rare kidney diseases. Grayson PC, Eddy S, Taroni JN, Lightfoot YL, Mariani L, Parikh H, Lindenmeyer MT, Ju W, Greene CS, Godfrey B, Cohen CD, Krischer J, Kretzler M, Merkel PA; Vasculitis Clinical Research Consortium, the European Renal cDNA Bank cohort, and the Nephrotic Syndrome Study Network. Ann Rheum Dis. 2018;77:1226-33. doi: 10.1136/annrheumdis-2017-212935. PMID: 29724730; PMCID: PMC6045442. 

Patient perceptions of glucocorticoids in anti-neutrophil cytoplasmic antibody-associated vasculitis. Robson JC, Dawson J, Cronholm PF, Ashdown S, Easley E, Kellom KS, Gebhart D, Lanier G, Milman N, Peck J, Luqmani RA, Shea JA, Tomasson G, Merkel PA. Rheumatol Int. 2018 Apr;38(4):675-682. doi: 10.1007/s00296-017-3855-6. Epub 2017 Nov 9.

Role of Macrophage Migration Inhibitory Factor in Granulomatosis With Polyangiitis. Sreih AG, Ezzedine R, Leng L, Fan J, Yao J, Reid D, Piecychna M, Carette S, Cuthbertson D, Dellaripa P, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Mahr A, McAlear CA, Maksimowicz-Mckinnon K, Monach PA, Seo P, Specks U, St Clair EW, Stone JH, Ytterberg SR, Edberg J, Merkel PA, Bucala R. Arthritis Rheumatol. 2018 Dec;70(12):2077-2086. doi: 10.1002/art.40655. Epub 2018 Oct 22.

Serum S100 Proteins as a Marker of Disease Activity in Large Vessel Vasculitis. Springer JM, Monach P, Cuthbertson D, Carette S, Khalidi NA, McAlear CA, Pagnoux C, Seo P, Warrington KJ, Ytterberg SR, Hoffman G, Langford C, Hamilton T, Foell D, Vogl T, Holzinger D, Merkel PA, Roth J, Hajj-Ali RA. J Clin Rheumatol. 2018 Oct;24(7):393-395. doi: 10.1097/RHU.0000000000000729.

Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis. Conklin LS, Merkel PA, Pachman LM, Parikh H, Tawalbeh S, Damsker JM, Cuthbertson DD, Morgan GA, Monach PA, Hathout Y, Nagaraju K, van den Anker J, McAlear CA, Hoffman EP. Steroids. 2018 Dec;140:159-166. doi: 10.1016/j.steroids.2018.10.008. Epub 2018 Oct 21.

Serum periostin as a biomarker in eosinophilic granulomatosis with polyangiitis. Rhee RL, Holweg CTJ, Wong K, Cuthbertson D, Carette S, Khalidi NA, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. PLoS One. 2018 Oct 11;13(10):e0205768. doi: 10.1371/journal.pone.0205768. eCollection 2018.

Validation of the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire. Robson JC, Dawson J, Doll H, Cronholm PF, Milman N, Kellom K, Ashdown S, Easley E, Gebhart D, Lanier G, Mills J, Peck J, Luqmani RA, Shea J, Tomasson G, Merkel PA. Ann Rheum Dis. 2018 Aug;77(8):1157-1164. doi: 10.1136/annrheumdis-2017-212713. Epub 2018 Apr 25.

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis. Carmona FD, Vaglio A, Mackie SL, Hernández-Rodríguez J, Monach PA, Castañeda S, Solans R, Morado IC, Narváez J, Ramentol-Sintas M, Pease CT, Dasgupta B, Watts R, Khalidi N, Langford CA, Ytterberg S, Boiardi L, Beretta L, Govoni M, Emmi G, Bonatti F, Cimmino MA, Witte T, Neumann T, Holle J, Schönau V, Sailler L, Papo T, Haroche J, Mahr A, Mouthon L, Molberg Ø, Diamantopoulos AP, Voskuyl A, Brouwer E, Daikeler T, Berger CT, Molloy ES, O'Neill L, Blockmans D, Lie BA, Mclaren P, Vyse TJ, Wijmenga C, Allanore Y, Koeleman BPC; Spanish CGA Group; UKGCA Consortium; Vasculitis Clinical Research Consortium, Barrett JH, Cid MC, Salvarani C, Merkel PA, Morgan AW, González-Gay MA, Martín J. Am J Hum Genet. 2017 Jan 5;100(1):64-74. doi: 10.1016/j.ajhg.2016.11.013. Epub 2016 Dec 29.

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. Arthritis Rheumatol. 2017 Apr;69(4):837-845. doi: 10.1002/art.40044. Epub 2017 Mar 3.

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. Arthritis Rheumatol. 2017 Apr;69(4):846-853. doi: 10.1002/art.40037. Epub 2017 Mar 8.

Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. Carmona FD, Coit P, Saruhan-Direskeneli G, Hernández-Rodríguez J, Cid MC, Solans R, Castañeda S, Vaglio A, Direskeneli H, Merkel PA, Boiardi L, Salvarani C, González-Gay MA, Martín J, Sawalha AH; Spanish GCA Study Group; Italian GCA Study Group; Turkish Takayasu Study Group; Vasculitis Clinical Research Consortium. Sci Rep. 2017 Mar 9;7:43953. doi: 10.1038/srep43953.

Assessment of Disease Activity in Large-vessel Vasculitis: Results of an International Delphi Exercise. Aydin SZ, Direskeneli H, Merkel PA; International Delphi on Disease Activity Assessment in Large-vessel Vasculitis. J Rheumatol. 2017 Dec;44(12):1928-1932. doi: 10.3899/jrheum.161269. Epub 2017 Sep 1.

Clinicians' perspective on key domains in ANCA-associated vasculitis: a Delphi exercise. Milman N, Boonen A, Tugwell P, Merkel PA; OMERACT Vasculitis Working Group. Scand J Rheumatol. 2017 Mar;46(2):112-117. doi: 10.1080/03009742.2016.1188980. Epub 2016 Jul 20.

Developing a Core Set of Outcome Measures for Behçet Disease: Report from OMERACT 2016. Hatemi G, Meara A, Ozguler Y, Direskeneli H, Mahr A, Easley E, Gurcan M, Davis T, Gul A, Yazici Y, Zottenberg K, Esatoglu SN, Erer B, Kamali S, Yazici H, Cronholm PF, Merkel PA. J Rheumatol. 2017 Nov;44(11):1750-1753. doi: 10.3899/jrheum.161352. Epub 2017 Apr 1.

Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016. Sreih AG, Alibaz-Oner F, Kermani TA, Aydin SZ, Cronholm PF, Davis T, Easley E, Gul A, Mahr A, McAlear CA, Milman N, Robson JC, Tomasson G, Direskeneli H, Merkel PA. J Rheumatol. 2017 Dec;44(12):1933-1937. doi: 10.3899/jrheum.161467. Epub 2017 Sep 1.

Experience With Direct-to-Patient Recruitment for Enrollment Into a Clinical Trial in a Rare Disease: A Web-Based Study. Krischer J, Cronholm PF, Burroughs C, McAlear CA, Borchin R, Easley E, Davis T, Kullman J, Carette S, Khalidi N, Koening C, Langford CA, Monach P, Moreland L, Pagnoux C, Specks U, Sreih AG, Ytterberg S, Merkel PA; Vasculitis Clinical Research Consortium. J Med Internet Res. 2017 Feb 28;19(2):e50. doi: 10.2196/jmir.6798.

Gastrointestinal aspects of vasculitides. Soowamber M, Weizman AV, Pagnoux C. Nat Rev Gastroenterol Hepatol. 2017 Mar;14(3):185-194. doi: 10.1038/nrgastro.2016.179. Epub 2016 Nov 23.

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Merkel PA, Xie G, Monach PA, Ji X, Ciavatta DJ, Byun J, Pinder BD, Zhao A, Zhang J, Tadesse Y, Qian D, Weirauch M, Nair R, Tsoi A, Pagnoux C, Carette S, Chung S, Cuthbertson D, Davis JC Jr, Dellaripa PF, Forbess L, Gewurz-Singer O, Hoffman GS, Khalidi N, Koening C, Langford CA, Mahr AD, McAlear C, Moreland L, Seo EP, Specks U, Spiera RF, Sreih A, St Clair EW, Stone JH, Ytterberg SR, Elder JT, Qu J, Ochi T, Hirano N, Edberg JC, Falk RJ, Amos CI, Siminovitch KA; Vasculitis Clinical Research Consortium. Arthritis Rheumatol. 2017 May;69(5):1054-1066. doi: 10.1002/art.40034. Epub 2017 Apr 6.

IgA antibodies to myeloperoxidase in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Oommen E, Hummel A, Allmannsberger L, Cuthbertson D, Carette S, Pagnoux C, Hoffman GS, Jenne DE, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland L, Seo P, Sreih A, Ytterberg SR, Merkel PA, Specks U, Monach PA; Vasculitis Clinical Research Consortium. Clin Exp Rheumatol. 2017 Mar-Apr;35 Suppl 103(1):98-101. Epub 2017 Mar 1.

OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody-associated Vasculitis. Robson JC, Tomasson G, Milman N, Ashdown S, Boonen A, Casey GC, Cronholm PF, Cuthbertson D, Dawson J, Direskeneli H, Easley E, Kermani TA, Farrar JT, Gebhart D, Lanier G, Luqmani RA, Mahr A, McAlear CA, Peck J, Shea B, Shea JA, Sreih AG, Tugwell PS, Merkel PA. J Rheumatol. 2017 Oct;44(10):1529-1535. doi: 10.3899/jrheum.161139. Epub 2017 Sep 1.

Patient-Reported Outcomes in Glomerular Disease. Selewski DT, Thompson A, Kovacs S, Papadopoulos EJ, Carlozzi NE, Trachtman H, Troost JP, Merkel PA, Gipson DS. Clin J Am Soc Nephrol. 2017 Jan 6;12(1):140-148. doi: 10.2215/CJN.13231215. Epub 2016 Jun 3.

Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Gopaluni S, Smith RM, Lewin M, McAlear CA, Mynard K, Jones RB, Specks U, Merkel PA, Jayne DR; RITAZAREM Investigators. Trials. 2017 Mar 7;18(1):112. doi: 10.1186/s13063-017-1857-z.

The OMERACT Core Domain Set for Outcome Measures for Clinical Trials in Polymyalgia Rheumatica. Mackie SL, Twohig H, Neill LM, Harrison E, Shea B, Black RJ, Kermani TA, Merkel PA, Mallen CD, Buttgereit F, Mukhtyar C, Simon LS, Hill CL; OMERACT PMR Working Group. J Rheumatol. 2017 Oct;44(10):1515-1521. doi: 10.3899/jrheum.161109. Epub 2017 Aug 1.

A small n sequential multiple assignment randomized trial design for use in rare disease research. Tamura RN, Krischer JP, Pagnoux C, Micheletti R, Grayson PC, Chen YF, Merkel PA. Contemp Clin Trials. 2016 Jan;46:48-51. doi: 10.1016/j.cct.2015.11.010. Epub 2015 Nov 14.

Development and validation of case-finding algorithms for the identification of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis in large healthcare administrative databases. Sreih AG, Annapureddy N, Springer J, Casey G, Byram K, Cruz A, Estephan M, Frangiosa V, George MD, Liu M, Parker A, Sangani S, Sharim R, Merkel PA; Vasculitis Patient-Powered Research Network. Pharmacoepidemiol Drug Saf. 2016 Dec;25(12):1368-1374. doi: 10.1002/pds.4116. Epub 2016 Nov 1.

The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis. Kermani TA, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, McKinnon-Maksimowicz K, McAlear CA, Monach PA, Seo P, Warrington KJ, Ytterberg SR, Merkel PA, Matteson EL; Vasculitis Clinical Research Consortium. J Rheumatol. 2016 Jun;43(6):1078-84. doi: 10.3899/jrheum.151063. Epub 2016 Apr 1.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.

Using patient-reported outcomes and PROMIS in research and clinical applications: experiences from the PCORI pilot projects. Bingham CO 3rd, Bartlett SJ, Merkel PA, Mielenz TJ, Pilkonis PA, Edmundson L, Moore E, Sabharwal RK. Qual Life Res. 2016 Aug;25(8):2109-16. doi: 10.1007/s11136-016-1246-1. Epub 2016 Feb 25.

Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients and systematic review of the literature. Sy A, Khalidi N, Dehghan N, Barra L, Carette S, Cuthbertson D, Hoffman GS, Koening CL, Langford CA, McAlear C, Moreland L, Monach PA, Seo P, Specks U, Sreih A, Ytterberg SR, Van Assche G, Merkel PA, Pagnoux C; Vasculitis Clinical Research Consortium (VCRC); Canadian Vasculitis Network (CanVasc). Semin Arthritis Rheum. 2016 Feb;45(4):475-82. doi: 10.1016/j.semarthrit.2015.07.006. Epub 2015 Jul 26.

Visual Complications in Patients with Biopsy-proven Giant Cell Arteritis: A Population-based Study. Saleh M, Turesson C, Englund M, Merkel PA, Mohammad AJ. J Rheumatol. 2016 Aug;43(8):1559-65. doi: 10.3899/jrheum.151033. Epub 2016 Jun 1.

A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility. Carmona FD, Mackie SL, Martín JE, Taylor JC, Vaglio A, Eyre S, Bossini-Castillo L, Castañeda S, Cid MC, Hernández-Rodríguez J, Prieto-González S, Solans R, Ramentol-Sintas M, González-Escribano MF, Ortiz-Fernández L, Morado IC, Narváez J, Miranda-Filloy JA; Spanish GCA Group, Beretta L, Lunardi C, Cimmino MA, Gianfreda D, Santilli D, Ramirez GA, Soriano A, Muratore F, Pazzola G, Addimanda O, Wijmenga C, Witte T, Schirmer JH, Moosig F, Schönau V, Franke A, Palm Ø, Molberg Ø, Diamantopoulos AP, Carette S, Cuthbertson D, Forbess LJ, Hoffman GS, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland L, Monach PA, Pagnoux C, Seo P, Spiera R, Sreih AG, Warrington KJ, Ytterberg SR, Gregersen PK, Pease CT, Gough A, Green M, Hordon L, Jarrett S, Watts R, Levy S, Patel Y, Kamath S, Dasgupta B, Worthington J, Koeleman BP, de Bakker PI, Barrett JH, Salvarani C, Merkel PA, González-Gay MA, Morgan AW, Martín J. Am J Hum Genet. 2015 Apr 2;96(4):565-80. doi: 10.1016/j.ajhg.2015.02.009. Epub 2015 Mar 26.

Cardiac Involvement in Granulomatosis with Polyangiitis. McGeoch L, Carette S, Cuthbertson D, Hoffman GS, Khalidi N, Koening CL, Langford CA, McAlear CA, Moreland L, Monach PA, Seo P, Specks U, Ytterberg SR, Merkel PA, Pagnoux C; Vasculitis Clinical Research Consortium. J Rheumatol. 2015 Jul;42(7):1209-12. doi: 10.3899/jrheum.141513. Epub 2015 May 1.

Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts. Pagnoux C, Carette S, Khalidi NA, Walsh M, Hiemstra TF, Cuthbertson D, Langford C, Hoffman G, Koening CL, Monach PA, Moreland L, Mouthon L, Seo P, Specks U, Ytterberg S, Westman K, Hoglund P, Harper L, Flossman O, Luqmani R, Savage CO, Rasmussen N, de Groot K, Tesar V, Jayne D, Merkel PA, Guillevin L; french Vasculitis Study Group (FVSG), European Vasculitis Society (EUVAS) and Vasculitis Clinical Research Consortium (VCRC). Clin Exp Rheumatol. 2015 Mar-Apr;33(2 Suppl 89):S-77-83. Epub 2015 May 26.

Current Status, Goals, and Research Agenda for Outcome Measures Development in Behçet Syndrome: Report from OMERACT 2014. Hatemi G, Ozguler Y, Direskeneli H, Mahr A, Gul A, Levi V, Aydin SZ, Mumcu G, Sertel-Berk O, Stevens RM, Yazici H, Merkel PA. J Rheumatol. 2015 Dec;42(12):2436-41. doi: 10.3899/jrheum.141147. Epub 2015 Sep 15.

Defining the nasal transcriptome in granulomatosis with polyangiitis (Wegener's). Grayson PC, Steiling K, Platt M, Berman JS, Zhang X, Xiao J, Alekseyev YO, Liu G, Monach PA, Kaplan MJ, Spira A, Merkel PA. Arthritis Rheumatol. 2015 May;67(8):2233-9. doi: 10.1002/art.39185.

Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study. Kermani TA, Warrington KJ, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, McAlear CA, Monach PA, Seo P, Merkel PA, Ytterberg SR; Vasculitis Clinical Research Consortium. J Rheumatol. 2015 Jul;42(7):1213-7. doi: 10.3899/jrheum.141347. Epub 2015 Apr 15.

Exploration, Development, and Validation of Patient-reported Outcomes in Antineutrophil Cytoplasmic Antibody-associated Vasculitis Using the OMERACT Process. Robson JC, Milman N, Tomasson G, Dawson J, Cronholm PF, Kellom K, Shea J, Ashdown S, Boers M, Boonen A, Casey GC, Farrar JT, Gebhart D, Krischer J, Lanier G, McAlear CA, Peck J, Sreih AG, Tugwell PS, Luqmani RA, Merkel PA. J Rheumatol. 2015 Nov;42(11):2204-9. doi: 10.3899/jrheum.141143. Epub 2015 Sep 1.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study. Renauer PA, Saruhan-Direskeneli G, Coit P, Adler A, Aksu K, Keser G, Alibaz-Oner F, Aydin SZ, Kamali S, Inanc M, Carette S, Cuthbertson D, Hoffman GS, Akar S, Onen F, Akkoc N, Khalidi NA, Koening C, Karadag O, Kiraz S, Langford CA, Maksimowicz-McKinnon K, McAlear CA, Ozbalkan Z, Ates A, Karaaslan Y, Duzgun N, Monach PA, Ozer HT, Erken E, Ozturk MA, Yazici A, Cefle A, Onat AM, Kisacik B, Pagnoux C, Kasifoglu T, Seyahi E, Fresko I, Seo P, Sreih AG, Warrington KJ, Ytterberg SR, Cobankara V, Cunninghame-Graham DS, Vyse TJ, Pamuk ON, Tunc SE, Dalkilic E, Bicakcigil M, Yentur SP, Wren JD, Merkel PA, Direskeneli H, Sawalha AH. Arthritis Rheumatol. 2015 May;67(5):1361-8. doi: 10.1002/art.39035.

Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Grayson PC, Carmona-Rivera C, Xu L, Lim N, Gao Z, Asare AL, Specks U, Stone JH, Seo P, Spiera RF, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Ytterberg SR, Phippard DJ, Merkel PA, Kaplan MJ, Monach PA; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Arthritis Rheumatol. 2015 Jul;67(7):1922-32. doi: 10.1002/art.39153.

Outcome measures for Takayasu's arteritis. Aydin SZ, Merkel PA, Direskeneli H. Curr Opin Rheumatol. 2015 Jan;27(1):32-7. doi: 10.1097/BOR.0000000000000129.

Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Dejaco C, Oppl B, Monach P, Cuthbertson D, Carette S, Hoffman G, Khalidi N, Koening C, Langford C, McKinnon-Maksimowicz K, Seo P, Specks U, Ytterberg S, Merkel PA, Zwerina J. PLoS One. 2015 Mar 26;10(3):e0121737. doi: 10.1371/journal.pone.0121737. eCollection 2015.

Update on Outcome Measure Development for Large Vessel Vasculitis: Report from OMERACT 12. Aydin SZ, Direskeneli H, Sreih A, Alibaz-Oner F, Gul A, Kamali S, Hatemi G, Kermani T, Mackie SL, Mahr A, Meara A, Milman N, Nugent H, Robson J, Tomasson G, Merkel PA. J Rheumatol. 2015 Dec;42(12):2465-9. doi: 10.3899/jrheum.141144. Epub 2015 Jun 15.

Value of commonly measured laboratory tests as biomarkers of disease activity and predictors of relapse in eosinophilic granulomatosis with polyangiitis. Grayson PC, Monach PA, Pagnoux C, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, Seo P, Specks U, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. Rheumatology (Oxford). 2015 Aug;54(8):1351-9. doi: 10.1093/rheumatology/keu427. Epub 2014 Nov 17.

An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Langford CA, Monach PA, Specks U, Seo P, Cuthbertson D, McAlear CA, Ytterberg SR, Hoffman GS, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. Ann Rheum Dis. 2014 Jul;73(7):1376-9. doi: 10.1136/annrheumdis-2013-204164. Epub 2013 Dec 9.

Biomarkers in vasculitis. Monach PA. Curr Opin Rheumatol. 2014 Jan;26(1):24-30. doi: 10.1097/BOR.0000000000000009.

Causal attributions about disease onset and relapse in patients with systemic vasculitis. Grayson PC, Amudala NA, McAlear CA, Leduc RL, Shereff D, Richesson R, Fraenkel L, Merkel PA. J Rheumatol. 2014 May;41(5):923-30. doi: 10.3899/jrheum.131096. Epub 2014 Mar 15.

Current status of outcome measure development in vasculitis. Merkel PA, Aydin SZ, Boers M, Cornell C, Direskeneli H, Gebhart D, Hatemi G, Luqmani R, Matteson EL, Milman N, Robson J, Seo P, Tomasson G. J Rheumatol. 2014 Mar;41(3):593-8. doi: 10.3899/jrheum.131248. Epub 2014 Jan 15.

Outcome measures used in clinical trials for Behçet syndrome: a systematic review. Hatemi G, Merkel PA, Hamuryudan V, Boers M, Direskeneli H, Aydin SZ, Yazici H. J Rheumatol. 2014 Mar;41(3):599-612. doi: 10.3899/jrheum.131249. Epub 2014 Feb 1.

The informational needs of patients with ANCA-associated vasculitis-development of an informational needs questionnaire. Mooney J, Spalding N, Poland F, Grayson P, Leduc R, McAlear CA, Richesson RL, Shereff D, Merkel PA, Watts RA. Rheumatology (Oxford). 2014 Aug;53(8):1414-21. doi: 10.1093/rheumatology/keu026. Epub 2014 Mar 12.

A monoclonal antibody (MCPR3-7) interfering with the activity of proteinase 3 by an allosteric mechanism. Hinkofer LC, Seidel SA, Korkmaz B, Silva F, Hummel AM, Braun D, Jenne DE, Specks U. J Biol Chem. 2013 Sep 13;288(37):26635-48. doi: 10.1074/jbc.M113.495770. Epub 2013 Jul 31.

Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. Xie G, Roshandel D, Sherva R, Monach PA, Lu EY, Kung T, Carrington K, Zhang SS, Pulit SL, Ripke S, Carette S, Dellaripa PF, Edberg JC, Hoffman GS, Khalidi N, Langford CA, Mahr AD, St Clair EW, Seo P, Specks U, Spiera RF, Stone JH, Ytterberg SR, Raychaudhuri S, de Bakker PI, Farrer LA, Amos CI, Merkel PA, Siminovitch KA. Arthritis Rheum. 2013 Sep;65(9):2457-68. doi: 10.1002/art.38036.

Churg-Strauss syndrome cardiac involvement evaluated by cardiac magnetic resonance imaging and positron-emission tomography: a prospective study on 20 patients. Marmursztejn J, Guillevin L, Trebossen R, Cohen P, Guilpain P, Pagnoux C, Mouthon L, Legmann P, Vignaux O, Duboc D. Rheumatology (Oxford). 2013 Apr;52(4):642-50. doi: 10.1093/rheumatology/kes155. Epub 2012 Jul 5.

Comment on: How common is inflammatory marker-negative disease in giant cell arteritis?. Kermani TA, Warrington KJ. Eye (Lond). 2013 May;27(5):677-8. doi: 10.1038/eye.2013.19. Epub 2013 Mar 8.

Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Schmidt J, Kermani TA, Bacani AK, Crowson CS, Cooper LT, Matteson EL, Warrington KJ. Mayo Clin Proc. 2013 Aug;88(8):822-30. doi: 10.1016/j.mayocp.2013.04.025. Epub 2013 Jul 10.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Comarmond C, Pagnoux C, Khellaf M, Cordier JF, Hamidou M, Viallard JF, Maurier F, Jouneau S, Bienvenu B, Puéchal X, Aumaître O, Le Guenno G, Le Quellec A, Cevallos R, Fain O, Godeau B, Seror R, Dunogué B, Mahr A, Guilpain P, Cohen P, Aouba A, Mouthon L, Guillevin L; French Vasculitis Study Group. Arthritis Rheum. 2013 Jan;65(1):270-81. doi: 10.1002/art.37721.

Fertility and pregnancy in vasculitis. Pagnoux C, Mahendira D, Laskin CA. Best Pract Res Clin Rheumatol. 2013 Feb;27(1):79-94. doi: 10.1016/j.berh.2013.02.002.

Identification of multiple genetic susceptibility loci in Takayasu arteritis. Saruhan-Direskeneli G, Hughes T, Aksu K, Keser G, Coit P, Aydin SZ, Alibaz-Oner F, Kamalı S, Inanc M, Carette S, Hoffman GS, Akar S, Onen F, Akkoc N, Khalidi NA, Koening C, Karadag O, Kiraz S, Langford CA, McAlear CA, Ozbalkan Z, Ates A, Karaaslan Y, Maksimowicz-McKinnon K, Monach PA, Ozer HT, Seyahi E, Fresko I, Cefle A, Seo P, Warrington KJ, Ozturk MA, Ytterberg SR, Cobankara V, Onat AM, Guthridge JM, James JA, Tunc E, Duzgun N, Bıcakcıgil M, Yentür SP, Merkel PA, Direskeneli H, Sawalha AH. Am J Hum Genet. 2013 Aug 8;93(2):298-305. doi: 10.1016/j.ajhg.2013.05.026. Epub 2013 Jul 3.

IgG4-related Disease: 2013 Update. Monach PA. Curr Treat Options Cardiovasc Med. 2013 Apr;15(2):214-23. doi: 10.1007/s11936-013-0232-y.

Illness perceptions and fatigue in systemic vasculitis. Grayson PC, Amudala NA, Mcalear CA, Leduc RL, Shereff D, Richesson R, Fraenkel L, Merkel PA. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1835-43. doi: 10.1002/acr.22069.

Is there a place for cyclophosphamide in the treatment of giant-cell arteritis? A case series and systematic review. de Boysson H, Boutemy J, Creveuil C, Ollivier Y, Letellier P, Pagnoux C, Bienvenu B. Semin Arthritis Rheum. 2013 Aug;43(1):105-12. doi: 10.1016/j.semarthrit.2012.12.023. Epub 2013 Feb 27.

L38. How to treat primary vasculitis of the central nervous system. Pagnoux C, de Boysson H. Presse Med. 2013 Apr;42(4 Pt 2):605-7. doi: 10.1016/j.lpm.2013.01.038. Epub 2013 Mar 1.

Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis. Kermani TA, Warrington KJ, Crowson CS, Ytterberg SR, Hunder GG, Gabriel SE, Matteson EL. Ann Rheum Dis. 2013 Dec;72(12):1989-94. doi: 10.1136/annrheumdis-2012-202408. Epub 2012 Dec 19.

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. Samson M, Puéchal X, Devilliers H, Ribi C, Cohen P, Stern M, Pagnoux C, Mouthon L, Guillevin L; French Vasculitis Study Group. J Autoimmun. 2013 Jun;43:60-9. doi: 10.1016/j.jaut.2013.03.003. Epub 2013 Apr 13.

New features of disease after diagnosis in 6 forms of systemic vasculitis. Grayson PC, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, Monach PA, Seo P, Specks U, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. J Rheumatol. 2013 Nov;40(11):1905-12. doi: 10.3899/jrheum.121473. Epub 2013 Aug 1.

Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Rothschild PR, Pagnoux C, Seror R, Brézin AP, Delair E, Guillevin L. Semin Arthritis Rheum. 2013 Apr;42(5):507-14. doi: 10.1016/j.semarthrit.2012.08.003. Epub 2012 Dec 24.

Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, De Zoysa J, Ives N, Clark WF, Quillen K, Winters JL, Wheatley K, Jayne D; PEXIVAS Investigators. Trials. 2013 Mar 14;14:73. doi: 10.1186/1745-6215-14-73.

Polymyalgia rheumatica. Kermani TA, Warrington KJ. Lancet. 2013 Jan 5;381(9860):63-72. doi: 10.1016/S0140-6736(12)60680-1. Epub 2012 Oct 8.

Pregnancy outcomes among patients with vasculitis. Clowse ME, Richeson RL, Pieper C, Merkel PA; Vasculitis Clinical Research Consortium. Arthritis Care Res (Hoboken). 2013 Aug;65(8):1370-4. doi: 10.1002/acr.21983.

Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Terrier B, Carrat F, Krastinova E, Marie I, Launay D, Lacraz A, Belenotti P, de Saint Martin L, Quemeneur T, Huart A, Bonnet F, Le Guenno G, Kahn JE, Hinschberger O, Rullier P, Hummel A, Diot E, Pagnoux C, Lzaro E, Bridoux F, Zenone T, Hermine O, Leger JM, Mariette X, Senet P, Plaisier E, Cacoub P. Ann Rheum Dis. 2013 Mar;72(3):374-80. doi: 10.1136/annrheumdis-2012-201405. Epub 2012 May 14.

Progressive multifocal encephalopathy after cyclophosphamide in granulomatosis with polyangiitis (Wegener) patients: case report and review of literature. Pugnet G, Pagnoux C, Bézanahary H, Ly KH, Vidal E, Guillevin L. Clin Exp Rheumatol. 2013 Jan-Feb;31(1 Suppl 75):S62-4. Epub 2013 Apr 22.

Quality of life and outcome measures in vasculitis. Tomasson G. Best Pract Res Clin Rheumatol. 2013 Feb;27(1):69-77. doi: 10.1016/j.berh.2013.01.003.

Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Mahr A, Katsahian S, Varet H, Guillevin L, Hagen EC, Höglund P, Merkel PA, Pagnoux C, Rasmussen N, Westman K, Jayne DR; French Vasculitis Study Group (FVSG) and the European Vasculitis Society (EUVAS). Ann Rheum Dis. 2013 Jun;72(6):1003-10. doi: 10.1136/annrheumdis-2012-201750. Epub 2012 Sep 8.

Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Iklé D, Kallenberg CG, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Ann Rheum Dis. 2013 Aug;72(8):1342-50. doi: 10.1136/annrheumdis-2012-201981. Epub 2012 Sep 12.

Temporal arteritis in the young. McGeoch L, Silecky WB, Maher J, Carette S, Pagnoux C. Joint Bone Spine. 2013 May;80(3):324-7. doi: 10.1016/j.jbspin.2012.09.012. Epub 2012 Nov 9.

Virus-Associated Vasculitides: An Update. Pagnoux C, Saadoun D. Pagnoux C, Saadoun D. Virus-Associated Vasculitides: An Update. Current Immunology Reviews. 2013 Feb. Volume 9, Number 1, February 2013, pp. 2-12(11).

urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Lieberthal JG, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, Seo P, Specks U, Ytterberg SR, Merkel PA, Monach PA; Vasculitis Clinical Research Consortium. J Rheumatol. 2013 May;40(5):674-83. doi: 10.3899/jrheum.120879. Epub 2013 Apr 1.

ANCA-associated diseases and lung carcinomas: a five-case series. Chemouny JM, Pagnoux C, Caudwell V, Karras A, Borie R, Guillevin L, Vrtovsnik F, Daugas E. Clin Nephrol. 2014 Feb;81(2):132-7. doi: 10.5414/CN107407.

Alveolar haemorrhage in ANCA-associated vasculitides: 80 patients' features and prognostic factors. Kostianovsky A, Hauser T, Pagnoux C, Cohen P, Daugas E, Mouthon L, Miossec P, Cordier JF, Guillevin L; French Vasculitis Study Group (FVSG). Clin Exp Rheumatol. 2012 Jan-Feb;30(1 Suppl 70):S77-82. Epub 2012 May 11.

Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's). Tomasson G, Boers M, Walsh M, LaValley M, Cuthbertson D, Carette S, Davis JC, Hoffman GS, Khalidi NA, Langford CA, McAlear CA, McCune WJ, Monach PA, Seo P, Specks U, Spiera R, St Clair EW, Stone JH, Ytterberg SR, Merkel PA. Arthritis Care Res (Hoboken). 2012 Feb;64(2):273-9. doi: 10.1002/acr.20649.

Association of vascular physical examination findings and arteriographic lesions in large vessel vasculitis. Grayson PC, Tomasson G, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Langford CA, McAlear CA, Monach PA, Seo P, Warrington KJ, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. J Rheumatol. 2012 Feb;39(2):303-9. doi: 10.3899/jrheum.110652. Epub 2011 Dec 15.

Capítulo 5: Tolerancia y Enfermedades Autoinmunitarias (Chapter 5:Tolerance and Autoimmune Disorders). Pujol R, Jaraquemada D, Rodríguez-Pla A. Tratado de Medicina Interna Farreras-Rozman (Internal Medicine Textbook Farreras-Rozman). XVII Edition. 2012; Rozman C, ed. Editorial Elsevier, Spain.

Challenging the diagnosis of primary angiitis of the central nervous system: a single-center retrospective study. Néel A, Auffray-Calvier E, Guillon B, Fontenoy AM, Loussouarn D, Pagnoux C, Hamidou MA. J Rheumatol. 2012 May;39(5):1026-34. doi: 10.3899/jrheum.110707. Epub 2012 Apr 1.

Churg-strauss syndrome: clinical symptoms, complementary investigations, prognosis and outcome, and treatment. Dunogué B, Pagnoux C, Guillevin L. Semin Respir Crit Care Med. 2011 Jun;32(3):298-309. doi: 10.1055/s-0031-1279826. Epub 2011 Jun 14.

Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis. Monach PA, Kümpers P, Lukasz A, Tomasson G, Specks U, Stone JH, Cuthbertson D, Krischer J, Carette S, Ding L, Hoffman GS, Iklé D, Kallenberg CG, Khalidi NA, Langford CA, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Haubitz M, Merkel PA. PLoS One. 2012;7(1):e30197. doi: 10.1371/journal.pone.0030197. Epub 2012 Jan 18.

Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis. Grayson PC, Maksimowicz-McKinnon K, Clark TM, Tomasson G, Cuthbertson D, Carette S, Khalidi NA, Langford CA, Monach PA, Seo P, Warrington KJ, Ytterberg SR, Hoffman GS, Merkel PA; Vasculitis Clinical Research Consortium. Ann Rheum Dis. 2012 Aug;71(8):1329-34. doi: 10.1136/annrheumdis-2011-200795. Epub 2012 Feb 10.

Exploiting multi-layered information to iteratively predict protein functions. Zhu W, Hou J, Chen YP. Math Biosci. 2012 Apr;236(2):108-16. doi: 10.1016/j.mbs.2012.02.004. Epub 2012 Mar 3.

Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients. Kostianovsky A, Charles P, Alves JF, Goulet M, Pagnoux C, Le Guern V, Mouthon L, Krivine A, Villiger P, Launay O, Guillevin L; French Vasculitis Study Group. Clin Exp Rheumatol. 2012 Jan-Feb;30(1 Suppl 70):S83-9. Epub 2012 May 11.

Life-threatening hepatitis C virus-associated polyarteritis nodosa successfully treated by rituximab. Néel A, Masseau A, Hervier B, Bossard C, Cacoub P, Pagnoux C, Hamidou MA. J Clin Rheumatol. 2011 Dec;17(8):439-41. doi: 10.1097/RHU.0b013e31823a58d7.

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis. Chung SA, Xie G, Roshandel D, Sherva R, Edberg JC, Kravitz M, Dellaripa PF, Hoffman GS, Mahr AD, Seo P, Specks U, Spiera RF, St Clair EW, Stone JH, Plenge RM, Siminovitch KA, Merkel PA, Monach PA. Arthritis Rheum. 2012 Oct;64(10):3463-71. doi: 10.1002/art.34496.

Pathogenesis of ANCA-associated vasculitis. Cartin-Ceba R, Peikert T, Specks U. Curr Rheumatol Rep. 2012 Dec;14(6):481-93. doi: 10.1007/s11926-012-0286-y.

Polyarteritis nodosa-like vasculitis in association with minocycline use: a single-center case series. Kermani TA, Ham EK, Camilleri MJ, Warrington KJ. Semin Arthritis Rheum. 2012 Oct;42(2):213-21. doi: 10.1016/j.semarthrit.2012.03.006. Epub 2012 Jun 15.

Recent advances in diagnostic strategies for giant cell arteritis. Kermani TA, Warrington KJ. Curr Neurol Neurosci Rep. 2012 Apr;12(2):138-44. doi: 10.1007/s11910-011-0243-6.

Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. Roubaud-Baudron C, Pagnoux C, Méaux-Ruault N, Grasland A, Zoulim A, LE Guen J, Prud'homme A, Bienvenu B, de Menthon M, Camps S, LE Guern V, Aouba A, Cohen P, Mouthon L, Guillevin L; French Vasculitis Study Group. J Rheumatol. 2012 Jan;39(1):125-30. doi: 10.3899/jrheum.110143. Epub 2011 Nov 15.

The Rare Diseases Clinical Research Network Contact Registry update: features and functionality. Richesson RL, Sutphen R, Shereff D, Krischer JP. Contemp Clin Trials. 2012 Jul;33(4):647-56. doi: 10.1016/j.cct.2012.02.012. Epub 2012 Mar 2.

Three unusual mimics of primary angiitis of the central nervous system. Shahane A, Khasnis A, Hajj Ali R. Rheumatol Int. 2012 Mar;32(3):737-42. doi: 10.1007/s00296-010-1679-8. Epub 2010 Dec 16.

Urogenital manifestations in Wegener granulomatosis: a study of 11 cases and review of the literature. Dufour JF, Le Gallou T, Cordier JF, Aumaître O, Pinède L, Aslangul E, Pagnoux C, Marie I, Puéchal X, Decaux O, Dubois A, Agard C, Mahr A, Comoz F, Boutemy J, Broussolle C, Guillevin L, Sève P, Bienvenu B; French Center-East Internists Group and the French Vasculitis Study Group. Medicine (Baltimore). 2012 Mar;91(2):67-74. doi: 10.1097/MD.0b013e318239add6.

Utility of erythrocyte sedimentation rate and C-reactive protein for the diagnosis of giant cell arteritis. Kermani TA, Schmidt J, Crowson CS, Ytterberg SR, Hunder GG, Matteson EL, Warrington KJ. Semin Arthritis Rheum. 2012 Jun;41(6):866-71. doi: 10.1016/j.semarthrit.2011.10.005. Epub 2011 Nov 25.

Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis--a meta-analysis. Tomasson G, Grayson PC, Mahr AD, Lavalley M, Merkel PA. Rheumatology (Oxford). 2012 Jan;51(1):100-9. doi: 10.1093/rheumatology/ker280. Epub 2011 Oct 29.

Vasculitis of the upper airways. Pagnoux C, Wolter NE. Swiss Med Wkly. 2012 Mar 19;142:w13541. doi: 10.4414/smw.2012.13541. eCollection 2012.

[Central nervous system vasculitides: an update]. Néel A, Pagnoux C, Guillevin L, Hamidou M. Rev Med Interne. 2012 Jul;33(7):381-9. doi: 10.1016/j.revmed.2011.11.020. Epub 2012 Jun 7.

A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis. Suppiah R, Judge A, Batra R, Flossmann O, Harper L, Höglund P, Javaid MK, Jayne D, Mukhtyar C, Westman K, Davis JC Jr, Hoffman GS, McCune WJ, Merkel PA, St Clair EW, Seo P, Spiera R, Stone JH, Luqmani R. Arthritis Care Res (Hoboken). 2011 Apr;63(4):588-96. doi: 10.1002/acr.20433.

Antineutrophil cytoplasmic antibodies, autoimmune neutropenia, and vasculitis. Grayson PC, Sloan JM, Niles JL, Monach PA, Merkel PA. Semin Arthritis Rheum. 2011 Dec;41(3):424-33. doi: 10.1016/j.semarthrit.2011.02.003. Epub 2011 Apr 19.

Assessment of disease activity and progression in Takayasu's arteritis. Direskeneli H, Aydin SZ, Merkel PA. Clin Exp Rheumatol. 2011 Jan-Feb;29(1 Suppl 64):S86-91. Epub 2011 May 11.

CNS involvement in acute posterior multifocal placoid pigment epitheliopathy. Pagnoux C, Thorne C, Mandelcorn ED, Carette S. Can J Neurol Sci. 2011 May;38(3):526-8. doi: 10.1017/s0317167100012002.

Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis. Monach PA, Tomasson G, Specks U, Stone JH, Cuthbertson D, Krischer J, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Ikle D, Kallenberg CG, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Gu YZ, Snyder RD, Merkel PA. Arthritis Rheum. 2011 Dec;63(12):3988-97. doi: 10.1002/art.30615.

DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans. Cao Y, Schmitz JL, Yang J, Hogan SL, Bunch D, Hu Y, Jennette CE, Berg EA, Arnett FC Jr, Jennette JC, Falk RJ, Preston GA. J Am Soc Nephrol. 2011 Jun;22(6):1161-7. doi: 10.1681/ASN.2010101058. Epub 2011 May 26.

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda. Direskeneli H, Aydin SZ, Kermani TA, Matteson EL, Boers M, Herlyn K, Luqmani RA, Neogi T, Seo P, Suppiah R, Tomasson G, Merkel PA. J Rheumatol. 2011 Jul;38(7):1471-9. doi: 10.3899/jrheum.110275.

Dorsal prevertebral lesions in Wegener granulomatosis: report on four cases. Barreto P, Pagnoux C, Luca L, Aouizerate J, Ortigueira I, Cohen P, Muller G, Guillevin L. Joint Bone Spine. 2011 Jan;78(1):88-91. doi: 10.1016/j.jbspin.2010.07.017. Epub 2010 Sep 18.

Encrusting cystitis due to Corynebacterium urealyticum in a patient with ANCA-associated vasculitis: case report and review of the literature. Pagnoux C, Bérezné A, Damade R, Paillot J, Aouizerate J, Le Guern V, Salmon D, Guillevin L. Semin Arthritis Rheum. 2011 Oct;41(2):297-300. doi: 10.1016/j.semarthrit.2010.11.004. Epub 2011 Feb 1.

Health-related quality of life in patients with newly diagnosed antineutrophil cytoplasmic antibody-associated vasculitis. Walsh M, Mukhtyar C, Mahr A, Herlyn K, Luqmani R, Merkel PA, Jayne DR. Arthritis Care Res (Hoboken). 2011 Jul;63(7):1055-61. doi: 10.1002/acr.20471.

Idiopathic retroperitoneal fibrosis: a retrospective review of clinical presentation, treatment, and outcomes. Kermani TA, Crowson CS, Achenbach SJ, Luthra HS. Mayo Clin Proc. 2011 Apr;86(4):297-303. doi: 10.4065/mcp.2010.0663.

IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic variants influences granulomatosis with polyangiitis. Kelley JM, Monach PA, Ji C, Zhou Y, Wu J, Tanaka S, Mahr AD, Johnson S, McAlear C, Cuthbertson D, Carette S, Davis JC Jr, Dellaripa PF, Hoffman GS, Khalidi N, Langford CA, Seo P, St Clair EW, Specks U, Stone JH, Spiera RF, Ytterberg SR, Merkel PA, Edberg JC, Kimberly RP. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20736-41. doi: 10.1073/pnas.1109227109. Epub 2011 Dec 6.

Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides. Le Guenno G, Mahr A, Pagnoux C, Dhote R, Guillevin L; French Vasculitis Study Group. Arthritis Rheum. 2011 May;63(5):1435-45. doi: 10.1002/art.30296.

Infliximab or rituximab for refractory Wegener's granulomatosis: long-term follow up. A prospective randomised multicentre study on 17 patients. de Menthon M, Cohen P, Pagnoux C, Buchler M, Sibilia J, Détrée F, Gayraud M, Khellaf M, Penalba C, Legallicier B, Mouthon L, Guillevin L. Clin Exp Rheumatol. 2011 Jan-Feb;29(1 Suppl 64):S63-71. Epub 2011 May 11.

Lower extremity vasculitis in polymyalgia rheumatica and giant cell arteritis. Kermani TA, Warrington KJ. Curr Opin Rheumatol. 2011 Jan;23(1):38-42. doi: 10.1097/BOR.0b013e3283410072.

Malignancy risk in vasculitis. Kermani TA, Warrington KJ, Amin S. Ther Adv Musculoskelet Dis. 2011 Feb;3(1):55-63. doi: 10.1177/1759720X10387460.

Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index. Suppiah R, Flossman O, Mukhtyar C, Alberici F, Baslund B, Brown D, Hasan N, Holle J, Hruskova Z, Jayne D, Judge A, Little MA, Merkel PA, Palmisano A, Seo P, Stegeman C, Tesar V, Vaglio A, Westman K, Luqmani R. Ann Rheum Dis. 2011 Jan;70(1):80-5. doi: 10.1136/ard.2009.122952. Epub 2010 Aug 24.

Nomenclature and classification of vasculitis - update on the ACR/EULAR diagnosis and classification of vasculitis study (DCVAS). Luqmani RA, Suppiah R, Grayson PC, Merkel PA, Watts R. Clin Exp Immunol. 2011 May;164 Suppl 1(Suppl 1):11-3. doi: 10.1111/j.1365-2249.2011.04358.x.

Patients with systemic inflammatory and autoimmune diseases are at risk of vaccine-preventable illnesses. Marchand-Janssen C, Loulergue P, Mouthon L, Mahr A, Blanche P, Deforges L, Lebon P, Cohen P, Pagnoux C, Le Guern V, Bienvenu B, Aouba A, Guillevin L, Launay O. Rheumatology (Oxford). 2011 Jun;50(6):1099-105. doi: 10.1093/rheumatology/keq422. Epub 2011 Jan 21.

Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, Haubitz M, Merkel PA, Peh CA, Pusey C, Jayne D. Am J Kidney Dis. 2011 Apr;57(4):566-74. doi: 10.1053/j.ajkd.2010.10.049. Epub 2010 Dec 30.

Pneumocystis jiroveci pneumonia in giant cell arteritis: A case series. Kermani TA, Ytterberg SR, Warrington KJ. Arthritis Care Res (Hoboken). 2011 May;63(5):761-5. doi: 10.1002/acr.20435.

Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies. Pagnoux C, Le Guern V, Goffinet F, Diot E, Limal N, Pannier E, Warzocha U, Tsatsaris V, Dhote R, Karras A, Cohen P, Damade R, Mouthon L, Guillevin L. Rheumatology (Oxford). 2011 May;50(5):953-61. doi: 10.1093/rheumatology/keq421. Epub 2010 Dec 22.

Relationship between markers of platelet activation and inflammation with disease activity in Wegener's granulomatosis. Tomasson G, Lavalley M, Tanriverdi K, Finkielman JD, Davis JC Jr, Hoffman GS, McCune WJ, St Clair EW, Specks U, Spiera R, Stone JH, Freedman JE, Merkel PA; Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. J Rheumatol. 2011 Jun;38(6):1048-54. doi: 10.3899/jrheum.100735. Epub 2011 Mar 16.

Sialylation levels of anti-proteinase 3 antibodies are associated with the activity of granulomatosis with polyangiitis (Wegener's). Espy C, Morelle W, Kavian N, Grange P, Goulvestre C, Viallon V, Chéreau C, Pagnoux C, Michalski JC, Guillevin L, Weill B, Batteux F, Guilpain P. Arthritis Rheum. 2011 Jul;63(7):2105-15. doi: 10.1002/art.30362.

Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's): long-term followup of a multicenter longitudinal cohort. Silva F, Seo P, Schroeder DR, Stone JH, Merkel PA, Hoffman GS, Spiera R, Sebastian JK, Davis JC Jr, St Clair EW, Allen NB, McCune WJ, Ytterberg SR, Specks U; Wegener's Granulomatosis Etanercept Trial Research Group. Arthritis Rheum. 2011 Aug;63(8):2495-503. doi: 10.1002/art.30394.

The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Toumelin PL; French Vasculitis Study Group (FVSG). Medicine (Baltimore). 2011 Jan;90(1):19-27. doi: 10.1097/MD.0b013e318205a4c6.

The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis. Merkel PA, Aydin SZ, Boers M, Direskeneli H, Herlyn K, Seo P, Suppiah R, Tomasson G, Luqmani RA. J Rheumatol. 2011 Jul;38(7):1480-6. doi: 10.3899/jrheum.110276.

The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis. Guilpain P, Chéreau C, Goulvestre C, Servettaz A, Montani D, Tamas N, Pagnoux C, Hachulla E, Weill B, Guillevin L, Mouthon L, Batteux F. Eur Respir J. 2011 Jun;37(6):1503-13. doi: 10.1183/09031936.00148409. Epub 2010 Nov 11.

Wegener's granulomatosis strictly and persistently localized to one organ is rare: assessment of 16 patients from the French Vasculitis Study Group database. Pagnoux C, Stubbe M, Lifermann F, Decaux O, Pavic M, Bérezné A, Delacroix-Szmania I, Méaux-Ruault N, Bienvenu B, Cabane J, Guillevin L; French Vasculitis Study Group. J Rheumatol. 2011 Mar;38(3):475-8. doi: 10.3899/jrheum.100518. Epub 2010 Dec 1.

Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis. Mahr AD, Edberg JC, Stone JH, Hoffman GS, St Clair EW, Specks U, Dellaripa PF, Seo P, Spiera RF, Rouhani FN, Brantly ML, Merkel PA. Arthritis Rheum. 2010 Dec;62(12):3760-7. doi: 10.1002/art.27742.

Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, Bienvenu B, Mouthon L, Guillevin L; French Vasculitis Study Group. Arthritis Rheum. 2010 Feb;62(2):616-26. doi: 10.1002/art.27240.

Discrimination and variable impact of ANCA binding to different surface epitopes on proteinase 3, the Wegener's autoantigen. Silva F, Hummel AM, Jenne DE, Specks U. J Autoimmun. 2010 Dec;35(4):299-308. doi: 10.1016/j.jaut.2010.06.021.

Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: A meta-analysis. Walsh M, Merkel PA, Mahr A, Jayne D. Arthritis Care Res (Hoboken). 2010 Aug;62(8):1166-73. doi: 10.1002/acr.20176.

Livedo reticularis and erythematous macules of the forearms indicating cutaneous microscopic polyangiitis. Dion J, Bachmeyer C, Moguelet P, Lescure FX, Pagnoux C. Am J Med. 2010 Nov;123(11):e5-6. doi: 10.1016/j.amjmed.2010.03.011.

Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement--a prospective, open-label pilot trial. Silva F, Specks U, Kalra S, Hogan MC, Leung N, Sethi S, Fervenza FC. Clin J Am Soc Nephrol. 2010 Mar;5(3):445-53. doi: 10.2215/CJN.06010809. Epub 2010 Jan 21.

Pathogenesis of ANCA-associated vasculitis. Flint J, Morgan MD, Savage CO. Rheum Dis Clin North Am. 2010 Aug;36(3):463-77. doi: 10.1016/j.rdc.2010.05.006. Epub 2010 Jun 23.

Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective. Herlyn K, Hellmich B, Seo P, Merkel PA. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1639-45. doi: 10.1002/acr.20276. Epub 2010 Jun 15.

Predictors at diagnosis of a first Wegener's granulomatosis relapse after obtaining complete remission. Pierrot-Deseilligny Despujol C, Pouchot J, Pagnoux C, Coste J, Guillevin L. Rheumatology (Oxford). 2010 Nov;49(11):2181-90. doi: 10.1093/rheumatology/keq244. Epub 2010 Jul 31.

Reporting of corticosteroid use in systemic disease trials: evidence from a systematic review of the potential impact on treatment effect. Pagnoux C, Dechartres A, Giraudeau B, Seror R, Guillevin L, Ravaud P. Arthritis Care Res (Hoboken). 2010 Jul;62(7):1002-8. doi: 10.1002/acr.20139.

Serum chitotriosidase activity and Wegener's granulomatosis. Koening CL, Gota CE, Langford CA, Hoffman GS, Natowicz MR. Clin Biochem. 2010 Mar;43(4-5):512-4. doi: 10.1016/j.clinbiochem.2009.11.015. Epub 2009 Dec 1.

Treatment strategies and outcome of induction-refractory Wegener's granulomatosis or microscopic polyangiitis: analysis of 32 patients with first-line induction-refractory disease in the WEGENT trial. Seror R, Pagnoux C, Ruivard M, Landru I, Wahl D, Rivière S, Aussant S, Mahr A, Cohen P, Mouthon L, Guillevin L; French Vasculitis Study Group. Ann Rheum Dis. 2010 Dec;69(12):2125-30. doi: 10.1136/ard.2010.131953. Epub 2010 Jul 19.

Assessment of damage in vasculitis: expert ratings of damage. Seo P, Jayne D, Luqmani R, Merkel PA. Rheumatology (Oxford). 2009 Jul;48(7):823-7. doi: 10.1093/rheumatology/kep103. Epub 2009 May 19.

Clinical research for rare disease: opportunities, challenges, and solutions. Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA; Rare Diseases Clinical Research Network. Mol Genet Metab. 2009 Jan;96(1):20-6. doi: 10.1016/j.ymgme.2008.10.003. Epub 2008 Nov 13.

Comparison of disease activity measures for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. Merkel PA, Cuthbertson DD, Hellmich B, Hoffman GS, Jayne DR, Kallenberg CG, Krischer JP, Luqmani R, Mahr AD, Matteson EL, Specks U, Stone JH; Vasculitis Clinical Research Consortium. Ann Rheum Dis. 2009 Jan;68(1):103-6. doi: 10.1136/ard.2008.097758. Epub 2008 Jul 29.

Glycosylation of proteinase 3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St Clair EW, Davis JC Jr, McCune WJ, Lears A, Ytterberg SR, Hummel AM, Viss MA, Peikert T, Stone JH, Specks U; WGET Research Group. Clin Exp Rheumatol. 2009 Jan-Feb;27(1 Suppl 52):S45-52.

Limited utility of rapamycin in severe, refractory Wegener's granulomatosis. Koening CL, Hernández-Rodríguez J, Molloy ES, Clark TM, Hoffman GS. J Rheumatol. 2009 Jan;36(1):116-9. doi: 10.3899/jrheum.080664.

MMP-12, a novel matrix metalloproteinase associated with giant cell arteritis. Rodríguez-Pla A, Martínez-Murillo F, Savino PJ, Eagle RC Jr, Seo P, Soloski MJ. Rheumatology (Oxford). 2009 Nov;48(11):1460-1. doi: 10.1093/rheumatology/kep271. Epub 2009 Sep 6.

Mimics of primary systemic vasculitides. Khasnis A, Molloy ES. International Journal of Clinical Rheumatology [Internet]. 2009; 4 5:[1-13 pp.]. DOI 10.2217/ijr.09.37.

Progress towards a core set of outcome measures in small-vessel vasculitis. Report from OMERACT 9. Merkel PA, Herlyn K, Mahr AD, Neogi T, Seo P, Walsh M, Boers M, Luqmani R. J Rheumatol. 2009 Oct;36(10):2362-8. doi: 10.3899/jrheum.090373.

Successful pregnancy and delivery of a healthy newborn despite transplacental transfer of antimyeloperoxidase antibodies from a mother with microscopic polyangiitis. Silva F, Specks U, Sethi S, Irazabal MV, Fervenza FC. Am J Kidney Dis. 2009 Sep;54(3):542-5. doi: 10.1053/j.ajkd.2009.02.016. Epub 2009 Apr 23.

Thromboembolic disease in vasculitis. Tomasson G, Monach PA, Merkel PA. Curr Opin Rheumatol. 2009 Jan;21(1):41-6. doi: 10.1097/BOR.0b013e32831de4e7.

Update on vasculitis. Khasnis A, Langford CA. J Allergy Clin Immunol. 2009 Jun;123(6):1226-36. doi: 10.1016/j.jaci.2009.04.024.

Assessment of the item selection and weighting in the Birmingham vasculitis activity score for Wegener's granulomatosis. Mahr AD, Neogi T, Lavalley MP, Davis JC, Hoffman GS, McCune WJ, Specks U, Spiera RF, St Clair EW, Stone JH, Merkel PA; Wegener's Granulomatosis Etanercept Trial Research Group. Arthritis Rheum. 2008 Jun 15;59(6):884-91. doi: 10.1002/art.23707.

Association of a nonsynonymous single-nucleotide polymorphism of matrix metalloproteinase 9 with giant cell arteritis. Rodríguez-Pla A, Beaty TH, Savino PJ, Eagle RC Jr, Seo P, Soloski MJ. Arthritis Rheum. 2008 Jun;58(6):1849-53. doi: 10.1002/art.23457.

Chapter 40: Polyarteritis Nodosa and other Necrotizing Systemic Vasculitis. Rodríguez-Pla A. Manual de Enfermedades Reumáticas de la Sociedad Española de Reumatología (Handbook of the Spanish Society of Rheumatology).  5ª Edición.  2008; JJ Gomez-Reino et. al., editores.  Editorial Médica Panamericana, S.A.

Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis. Wung PK, Anderson T, Fontaine KR, Hoffman GS, Specks U, Merkel PA, Spiera R, Davis JC, St Clair EW, McCune WJ, Stone JH; WEGENER'S GRANULOMATOSIS ETANERCEPT TRIAL RESEARCH GROUP. Arthritis Rheum. 2008 May 15;59(5):746-753. doi: 10.1002/art.23561.

Takayasu's arteritis. Koening CL, Langford CA. Curr Treat Options Cardiovasc Med. 2008 Apr;10(2):164-72. doi: 10.1007/s11936-008-0018-9.

The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study. Hauser T, Mahr A, Metzler C, Coste J, Sommerstein R, Gross WL, Guillevin L, Hellmich B. Thorax. 2008 Aug;63(8):677-82. doi: 10.1136/thx.2007.087825. Epub 2008 Feb 14.

Wegener Granulomatosis. Silva F, Lynch JP, Fishbein MC, Specks U. In “Interstitial Pulmonary and Bronchiolar Disorders, (Lynch JP III, Ed). InformaUSA, NY. 2008; volume 227; pp 605-642.

Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Mahr AD, Jover JA, Spiera RF, Hernández-García C, Fernández-Gutiérrez B, Lavalley MP, Merkel PA. Arthritis Rheum. 2007 Aug;56(8):2789-97. doi: 10.1002/art.22754.

Antiendothelial cell antibodies in patients with Wegener's granulomatosis: prevalence and correlation with disease activity and manifestations. Sebastian JK, Mahr AD, Ahmed SS, Stone JH, Romay-Penabad Z, Davis JC, Hoffman GS, McCune WJ, St Clair EW, Specks U, Spiera R, Pierangeli S, Merkel PA. J Rheumatol. 2007 May;34(5):1027-31. Epub 2007 Apr 15.

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott DG, Witter J, Yazici H, Luqmani RA. Ann Rheum Dis. 2007 May;66(5):605-17. doi: 10.1136/ard.2006.062711. Epub 2006 Dec 14.

Proposal to decrease the number of negative temporal artery biopsies. Rodríguez-Pla A, Rosselló-Urgell J, Bosch-Gil JA, Huguet-Redecilla P, Vilardell-Tarres M. Scand J Rheumatol. 2007 Mar-Apr;36(2):111-8. doi: 10.1080/03009740600991646.

The future of damage assessment in vasculitis. Seo P, Luqmani RA, Flossmann O, Hellmich B, Herlyn K, Hoffman GS, Jayne D, Kallenberg CG, Langford CA, Mahr A, Matteson EL, Mukhtyar CB, Neogi T, Rutgers A, Specks U, Stone JH, Ytterberg SR, Merkel PA. J Rheumatol. 2007 Jun;34(6):1357-71.

Novel therapeutic strategies for large vessel vasculitis. Koening CL, Langford CA. Rheum Dis Clin North Am. 2006 Feb;32(1):173-86, xi. doi: 10.1016/j.rdc.2005.09.006.

Use of SNOMED CT to represent clinical research data: a semantic characterization of data items on case report forms in vasculitis research. Richesson RL, Andrews JE, Krischer JP. J Am Med Inform Assoc. 2006 Sep-Oct;13(5):536-46. doi: 10.1197/jamia.M2093. Epub 2006 Jun 23.

Current status of outcome measures in vasculitis: focus on Wegener's granulomatosis and microscopic polyangiitis. Report from OMERACT 7. Merkel PA, Seo P, Aries P, Neogi T, Villa-Forte A, Boers M, Cuthbertson D, Felson DT, Hellmich B, Hoffman GS, Jayne DR, Kallenberg CG, Krischer J, Mahr A, Matteson EL, Specks U, Luqmani R, Stone J; Vasculitis Clinical Research Consortium; OMERACT 7 Special Interest Group. J Rheumatol. 2005 Dec;32(12):2488-95.

Metalloproteinase-2 and -9 in giant cell arteritis: involvement in vascular remodeling. Rodríguez-Pla A, Bosch-Gil JA, Rosselló-Urgell J, Huguet-Redecilla P, Stone JH, Vilardell-Tarres M. Circulation. 2005 Jul 12;112(2):264-9. doi: 10.1161/CIRCULATIONAHA.104.520114. Epub 2005 Jul 5.