{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:42:15Z","timestamp":1778751735321,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T00:00:00Z","timestamp":1468281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003756","name":"Biomedicum Helsinki-s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["016.130.664"],"award-info":[{"award-number":["016.130.664"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91613008"],"award-info":[{"award-number":["91613008"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0900747 91070"],"award-info":[{"award-number":["G0900747 91070"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Intellectual disability (ID) is a major health problem in our society. Genetic causes of <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> remain unknown because of its vast heterogeneity. Here we report two Finnish families and one Dutch family with affected individuals presenting with mild to moderate ID, neuropsychiatric symptoms and delayed speech development. By utilizing whole exome sequencing (WES), we identified a founder missense variant c.<jats:styled-content style=\"fixed-case\">983T<\/jats:styled-content>&gt;C (p.<jats:styled-content style=\"fixed-case\">Leu328Pro<\/jats:styled-content>) in seven affected individuals from two Finnish consanguineous families and a deletion c.799_1034\u2010<jats:styled-content style=\"fixed-case\">429delinsTTATGA<\/jats:styled-content> (p.Gln267fs) in one affected individual from a consanguineous Dutch family in the <jats:italic>C12orf4<\/jats:italic> gene on chromosome 12. Both the variants co\u2010segregated in the respective families as an autosomal recessive trait. Screening of the p.<jats:styled-content style=\"fixed-case\">Leu328Pro<\/jats:styled-content> variant showed enrichment in the North Eastern sub\u2010isolate of Finland among anonymous local blood donors with a carrier frequency of 1:53, similar to other disease mutations with a founder effect in that region. To date, only one Arab family with a three affected individuals with a frameshift insertion variant in <jats:italic>C12orf4<\/jats:italic> has been reported. In summary, we expand and establish the clinical and mutational spectrum of <jats:italic>C12orf4<\/jats:italic> variants. Our findings implicate <jats:italic>C12orf4<\/jats:italic> as a causative gene for autosomal recessive ID.<\/jats:p>","DOI":"10.1111\/cge.12821","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T10:57:06Z","timestamp":1466161026000},"page":"100-105","source":"Crossref","is-referenced-by-count":19,"title":["Identification of <i>C12orf4<\/i> as a gene for autosomal recessive intellectual disability"],"prefix":"10.1111","volume":"91","author":[{"given":"A.K.","family":"Philips","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Pinelli","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Centre  Nijmegen the Netherlands"},{"name":"The Telethon Institute of Genetics and Medicine (TIGEM)  Naples 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Netherlands"},{"name":"Department of Biochemistry University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University of Molecular Sciences, Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Roepman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University of Molecular Sciences, Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-3205","authenticated-orcid":false,"given":"J.S.","family":"Moilanen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, PEDEGO Research Unit and Medical Research Center Oulu Oulu University Hospital and University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Varilo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Scala","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 Degli Studi di Napoli \u201cFederico II\u201d  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Cocozza","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 Degli Studi di Napoli \u201cFederico II\u201d  Naples 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