{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:54:39Z","timestamp":1772826879457,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>TAF1C (TATA box\u2010binding protein\u2010associated factor, RNA polymerase I subunit C) is an essential component of the RNA polymerase I transcription machinery responsible for ribosomal RNA synthesis and nucleolar function. Variants in <jats:italic>TAF1C<\/jats:italic> have recently emerged as rare genetic causes of early\u2010onset neurological syndromes characterized by nucleolar stress and impaired ribosome biogenesis, leading to developmental delay and brain atrophy. Here, we report a novel homozygous missense variant (c.1766C&gt;T; p.Ser589Leu) in <jats:italic>TAF1C<\/jats:italic> in a 3\u2010year 8\u2010month\u2010old boy who exhibited normal development until age two, followed by generalized seizures and progressive neurodevelopmental regression, spasticity, microcephaly, and cerebellar atrophy. MRI revealed asymmetric diffusion restriction and diffuse cerebellar atrophy. Although the mutant <jats:italic>TAF1C<\/jats:italic> transcript and protein were expressed at normal levels in peripheral blood cells, immunofluorescence analysis revealed a loss of nucleolar localization and the formation of abnormal thread\u2010like aggregates within the nucleoplasm. These findings suggest that the p.Ser589Leu variant causes disease through functional mislocalization rather than loss of expression. Our case expands the phenotypic and mechanistic spectrum of <jats:italic>TAF1C<\/jats:italic>\u2010related disorders and highlights the importance of proper subnuclear localization for maintaining neuronal function and development.<\/jats:p>","DOI":"10.1111\/cge.14771","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T05:58:53Z","timestamp":1747288733000},"page":"594-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel <i>TAF1C<\/i> Missense Variant Causes Neurodevelopmental Regression via Disrupted Nucleolar Localization and Nucleoplasmic Aggregation"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5238","authenticated-orcid":false,"given":"S. Rehan","family":"Ahmad","sequence":"first","affiliation":[{"name":"Hiralal Mazumdar Memorial College for Women West Bengal State University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natchimuthu","family":"Vijayakumar","sequence":"additional","affiliation":[{"name":"M.Kumarasamy College of Engineering  Karur Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazim","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus King Khalid University (KKU)  Abha Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn987"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10141"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13827"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2054"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.240790"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-023-01026-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3461-5_5"},{"key":"e_1_2_9_9_1","first-page":"564","article-title":"Aberrant Phase Separation and Nucleolar Dysfunction in Rare Genetic Diseases","volume":"614","author":"Mensah M. A.","year":"2023","journal-title":"Nature"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells1040774"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T07:47:23Z","timestamp":1759823243000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/cge.14771"],"URL":"https:\/\/doi.org\/10.1111\/cge.14771","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]},"assertion":[{"value":"2025-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}