{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:19:07Z","timestamp":1789165147659,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Trichothiodystrophy (TTD) is caused by homozygous or compound heterozygous variants in genes associated with DNA repair. The\n ERCC2<\/jats:italic>\n gene encoded a protein, XPD, that is a subunit of the general transcription factor TFIIH and important in both DNA repair and transcription. Disease\u2010causing variants in\n ERCC2<\/jats:italic>\n can partially inactivate these activities, giving rise to symptoms seen in TTD, Cockayne syndrome (CS) and xeroderma pigmentosa (XP). Although generalized cerebral white matter abnormalities is reported in TTD, myelination disorders specifically linked to\n ERCC2<\/jats:italic>\n gene variants are exceptionally uncommon. Here, we introduce a thorough investigation of a patient exhibiting classic TTD symptoms alongside progressive cerebral hypomyelination with\n ERCC2<\/jats:italic>\n variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In a non\u2010consanguineous family, we conducted Autism\/ID gene Panel on a 5\u2010year\u2010old affected child who presented with microcephaly, failure to thrive, developmental delay, and progressive hypomyelination on three serial brain imaging over 5\u2010years follow\u2010up. Our investigation aimed to elucidate the genetic underpinnings of the observed phenotype. We also conducted a comprehensive review of the genetic profiles of all documented\n ERCC2<\/jats:italic>\n \u2010related patients exhibiting myelination disorders.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Autism\/ID gene Panel identified a compound heterozygous variant in\n ERCC2<\/jats:italic>\n gene causing TTD. Clinical and paraclinical findings enabled differentiation of TTD from Cockayne syndrome and XP. Segregation analysis revealed that, the variation in the paternal allele was a splice junction loss (c.2190\u2009+\u20091delG), and the other alteration in the maternal allele was a pathogenic variant (c.1479\u2009+\u20092dupT). It has been noted that these variants were reported in previous studies in homozygous or compound heterozygous form in patients with TTD, but none of them exhibited hypomyelinating leukodystrophy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The identification of hypomyelination in TTD due to\n ERCC2<\/jats:italic>\n sheds a light on the molecular diagnosis and contributing to the limited literature on\n ERCC2<\/jats:italic>\n variants and associated hypomyelinating leukodystrophy in patients with TTD.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70067","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T08:24:06Z","timestamp":1740039846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trichothiodystrophy due to\n ERCC2<\/i>\n Variants: Uncommon Contributor to Progressive Hypomyelinating Leukodystrophy"],"prefix":"10.1002","volume":"13","author":[{"given":"Ali Reza","family":"Tavasoli","sequence":"first","affiliation":[{"name":"Neurology Division Barrow Neurological Institute, Phoenix Children's Phoenix Arizona USA"},{"name":"Myelin Disorders Clinic, Children's Medical Center, Pediatric Center of Excellence Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arastoo","family":"Kaki","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medicine Hamadan University of Medical Sciences Hamadan Iran"},{"name":"Research Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute Hamadan University of Medical Sciences Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maedeh","family":"Ganji","sequence":"additional","affiliation":[{"name":"DeNA Genetics Laboratory Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyyed Mohammad","family":"Kahani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Tarbiat Modares University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foozhan","family":"Radmehr","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine National Institute of Genetic Engineering and Biotechnology Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-0910","authenticated-orcid":false,"given":"Pouria","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic, Children's Medical Center, Pediatric Center of Excellence Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Medical Genetics Tarbiat Modares University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Heidari","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic, Children's Medical Center, Pediatric Center of Excellence Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Reza","family":"Ashrafi","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic, Children's Medical Center, Pediatric Center of Excellence Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara S.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Neurology Division Barrow Neurological Institute, Phoenix Children's Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01603.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20912"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20768"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694\u2010189"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22087"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097\u20102765(00)80098\u20102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.058743"},{"key":"e_1_2_10_9_1","first-page":"89","article-title":"Brittle Hair, Photosensitivity, Brain Hypomyelination and Immunodeficiency: Clues to Trichothiodystrophy","volume":"84","author":"Farmaki E.","year":"2017","journal-title":"Journal of Theoretical 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