{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:19:40Z","timestamp":1791083980614,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine of the National Kapodistrian University of Athens"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified using Whole-Exome Sequencing (WES) in an 8.5-year-old boy with clinical symptoms similar to IOTH. The patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones, as well as some notable phenotypic characteristics, such as macrocephaly and macrosomia. Despite the absence of early neuroimaging, genetic testing revealed a paternally inherited variant in TMEM63A (NM_14698.3:c.220A&gt;T;p:(Arg74*)), potentially linked to infantile transient hypomyelinating leukodystrophy type 19. Our findings in this study and the patient\u2019s favorable clinical course underscore the potential for successful myelination even with delayed initiation and may contribute to a better understanding of the genotype\u2013phenotype correlation in IOTH, emphasizing the importance of genetic analysis in unresolved developmental delay cases and providing critical insights for accurate diagnosis, prognosis and potential therapeutic strategies in rare leukodystrophies.<\/jats:p>","DOI":"10.3390\/genes15050525","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T03:20:41Z","timestamp":1713842441000},"page":"525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A TMEM63A Nonsense Heterozygous Variant Linked to Infantile Transient Hypomyelinating Leukodystrophy Type 19?"],"prefix":"10.3390","volume":"15","author":[{"given":"Dimitra","family":"Siori","sequence":"first","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-6102","authenticated-orcid":false,"given":"Dimitrios","family":"Vlachakis","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece"},{"name":"School of Informatics, Faculty of Natural & Mathematical Sciences, King\u2019s College London, Bush House, Strand, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis","family":"Makrythanasis","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Department of Genetic Medicine and Development, Medical School, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-5628","authenticated-orcid":false,"given":"Joanne","family":"Traeger-Synodinos","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-0928","authenticated-orcid":false,"given":"Danai","family":"Veltra","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrodite","family":"Kampouraki","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/S1474-4422(19)30143-7","article-title":"Diagnosis, prognosis, and treatment of leukodystrophies","volume":"18","author":"Schiffmann","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41582-020-00432-1","article-title":"Hypomyelinating leukodystrophies-unravelling myelin biology","volume":"17","author":"Wolf","year":"2021","journal-title":"Nat. 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