{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:57:46Z","timestamp":1764331066864,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"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":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010linked intellectual disability type Nascimento (XIDTN) is a disorder of the ubiquitin\u2010proteasome pathway of protein degradation controlled by the <jats:italic>UBE2A<\/jats:italic> gene. The disease is characterized by intellectual disability, speech impairment, dysmorphic facial features, skin and nail anomalies, and, frequently, seizures. Eight affected males from a four\u2010generation family who have intellectual disability and speech disorders were examined within an extended family of 57 individuals.<\/jats:p><jats:p>Methods<\/jats:p><jats:p>A number of methods were used for the molecular diagnosis. Conventional karyotype analyses, array\u2010based comparative genomic hybridization (aCGH), whole exome swquencing (WES), sanger sequencing were performed.<\/jats:p><jats:p>Results<\/jats:p><jats:p>First, the conventional karyotype analyses were normal, and the results of the aCGH analyses were normal. Then, WES revealed a novel missense mutation of the <jats:italic>UBE2A<\/jats:italic> gene at exon 4 NM_003336.3: c.182A&gt;G (p.Glu61Gly). Seven affected individuals and nine carriers in the multigenerational, large family were diagnosed through Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified the mutation causing intellectual disability in the large family and demonstrated its phenotypic effects. Our cases showed that dysmorphic features could be considered mild, whereas intellectual disability and speech disorders are common features in XIDTN. The structure and function of the gene will be better understood in the novel <jats:italic>UBE2A<\/jats:italic> mutation. The genotype\u2013phenotype correlation and phenotypic variations in XIDTN were identified through a literature review. Accordingly, XIDTN should be considered in individuals who exhibit an X\u2010linked pedigree pattern and have intellectual disability and speech disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3307","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:11:03Z","timestamp":1608941463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel missense mutation in the <i>UBE2A<\/i> gene causes intellectual disability in the large X\u2010linked family"],"prefix":"10.1002","volume":"23","author":[{"given":"Saide Bet\u00fcl","family":"Arslan Sat\u0131lm\u0131\u015f","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Ankara City Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emin Emre","family":"Kurt","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara City Hospital  Ankara Turkey"},{"name":"Department of Medical Genetics Ankara Y\u0131ld\u0131r\u0131m Beyazit University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebru Perim","family":"Ak\u00e7ay","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Kocaeli University  Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-4848","authenticated-orcid":false,"given":"Ali","family":"Sazci","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Kocaeli University  Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4938-3420","authenticated-orcid":false,"given":"Ahmet Cevdet","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara City Hospital  Ankara Turkey"},{"name":"Department of Medical Genetics Ankara Y\u0131ld\u0131r\u0131m Beyazit University  Ankara 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