{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:30:49Z","timestamp":1786437049984,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019345","name":"King Salman Center for Disability Research","doi-asserted-by":"publisher","award":["2180 004"],"award-info":[{"award-number":["2180 004"]}],"id":[{"id":"10.13039\/501100019345","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2180 004"],"award-info":[{"award-number":["2180 004"]}],"id":[{"id":"https:\/\/ror.org\/01ht2b307","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["5932"],"award-info":[{"award-number":["5932"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5932"],"award-info":[{"award-number":["5932"]}],"id":[{"id":"https:\/\/ror.org\/01q3tbs38","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neurodevelopmental disorders (NDDs) are a group of conditions that impair the development and function of the central nervous system. Recently, variants in the EZH1 gene have been associated with neurodevelopmental disorders. Here, using whole-exome sequencing coupled with confirmatory Sanger sequencing, we identified a homozygous nonsense variant in EZH1 in two affected siblings. Both parents were heterozygous carriers of the variant. The variant is predicted to result in a 44-amino acid C-terminal truncation within the catalytic SET domain, leading to loss of protein function. RT-qPCR analysis revealed significantly reduced EZH1 mRNA expression in patient-derived peripheral blood cells. The index patient (female) also exhibited elevated gamma-glutamyl transferase (GGT) levels and hypoalbuminemia, whereas the affected male presented with central precocious puberty. This study further expands the clinical, genetic, and molecular spectrum of EZH1-associated neurodevelopmental disorders by demonstrating that reduced EZH1 expression is consistent with a loss-of-function disease mechanism.<\/jats:p>","DOI":"10.3390\/ijms27167087","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T10:12:01Z","timestamp":1786097521000},"page":"7087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic EZH1 Nonsense Novel Variant in Two Siblings with Neurodevelopmental Disorder and Central Precocious Puberty: A Case Report from a Consanguineous Saudi Family"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6895-2763","authenticated-orcid":false,"given":"Mohamed","family":"Baity","sequence":"first","affiliation":[{"name":"Translational Genomics Department, Genomic Medicine Center of Excellence, King Faisal Specialist Hospital, and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Clincial Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"},{"name":"Jazan Specialist Hospital, Jazan 82513, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-5033","authenticated-orcid":false,"given":"Khalid","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Clincial Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"AlObeid","sequence":"additional","affiliation":[{"name":"Translational Genomics Department, Genomic Medicine Center of Excellence, King Faisal Specialist Hospital, and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albandary","family":"AlBakheet","sequence":"additional","affiliation":[{"name":"Translational Genomics Department, Genomic Medicine Center of Excellence, King Faisal Specialist Hospital, and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Mahnashi","sequence":"additional","affiliation":[{"name":"King Fahd Central Hospital, Jazan 82666, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Arishi","sequence":"additional","affiliation":[{"name":"King Fahd Central Hospital, Jazan 82666, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Tohary","sequence":"additional","affiliation":[{"name":"King Fahd Central Hospital, Jazan 82666, Saudi Arabia"},{"name":"Medical Genomics Department, Genomic Medicine Center of Excellence, King Faisal Specialist Hospital, and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-0668","authenticated-orcid":false,"given":"Stefan T.","family":"Arold","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Division, KAUST Center of Excellence for Smart Health, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-8768","authenticated-orcid":false,"given":"Dilek","family":"Colak","sequence":"additional","affiliation":[{"name":"Colak Lab, Research and Innovation, King Faisal Specialist Hospital, and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-7507","authenticated-orcid":false,"given":"Namik","family":"Kaya","sequence":"additional","affiliation":[{"name":"Translational Genomics Department, Genomic Medicine Center of Excellence, King Faisal Specialist Hospital, and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Clincial Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/jnc.15168","article-title":"Recent advances in gene therapy for neurodevelopmental disorders with epilepsy","volume":"157","author":"Turner","year":"2021","journal-title":"J. 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