{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:01:43Z","timestamp":1788454903261,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n The RAR\u2010related orphan receptor alpha (\n RORA<\/jats:italic>\n ) gene encodes a nuclear receptor involved in transcriptional regulation, circadian rhythm, and neurodevelopment. Dominant\n RORA<\/jats:italic>\n variants are associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia, yet the phenotypic spectrum remains poorly defined. We performed comprehensive genetic and clinical analyses in four individuals with\n RORA<\/jats:italic>\n variants from three unrelated families, using whole exome sequencing and chromosomal microarray analysis. Identified variants were confirmed by Sanger sequencing. Genetic analyses revealed three distinct\n \n RORA<\/jats:italic>\n <\/jats:styled-content>\n variants: a 15q21.2\u2013q22.2 deletion encompassing\n \n RORA<\/jats:italic>\n <\/jats:styled-content>\n , a de novo nonsense variant c.\n 499C<\/jats:styled-content>\n >T (p.Gln167*), and a novel heterozygous frameshift variant c.683_686del (p.\n Glu228Valfs<\/jats:styled-content>\n *78) segregating within a family. Clinical findings ranged from severe neurodevelopmental delay and epilepsy to mild intellectual disability and behavioral abnormalities, demonstrating marked intrafamilial variability. Notably, the same frameshift variant presented with differing phenotypes in the family, indicating variable expressivity\u2014the first such observation reported in\n \n RORA<\/jats:italic>\n <\/jats:styled-content>\n \u2010related disorders. Our findings broaden the genotypic and phenotypic spectrum of\n RORA<\/jats:italic>\n \u2010related neurodevelopmental disorders. The observed intrafamilial variability highlights the complexity of RORA\u2010associated pathogenesis and underscores the importance of considering variable expressivity in future genotype\u2013phenotype studies.\n <\/jats:p>","DOI":"10.1111\/cge.70120","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T02:17:03Z","timestamp":1765592223000},"page":"951-956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel\n \n RORA<\/i>\n <\/scp>\n Variants Reveal Genotype\u2013Phenotype Diversity and Variable Expressivity in Neurodevelopmental Disorders"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4574-421X","authenticated-orcid":false,"given":"Gul","family":"Unsel\u2010Bolat","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Faculty of Medicine Bal\u0131kesir University Bal\u0131kesir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6574-8149","authenticated-orcid":false,"given":"Hilmi","family":"Bolat","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Bal\u0131kesir University Bal\u0131kesir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-4712","authenticated-orcid":false,"given":"Senol","family":"Citli","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Recep Tayyip Erdogan University Rize Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2441-8629","authenticated-orcid":false,"given":"Ozlem","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Private Clinics of Child Neurology Bursa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-3259","authenticated-orcid":false,"given":"Ibrahim","family":"Baris","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Ko\u00e7 University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"4","key":"e_1_2_8_2_1","first-page":"263","article-title":"Distinct Autism Spectrum Disorder Phenotype and Hand\u2010Flapping Stereotypes: Two Siblings With Novel Homozygous Mutation in TRAPPC9 Gene and Literature Review","volume":"13","author":"Bolat H.","year":"2022","journal-title":"Molecular 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