{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:58:25Z","timestamp":1791928705602,"version":"4.3.4"},"reference-count":41,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2013,9,7]]},"published-print":{"date-parts":[[2013,12]]},"abstract":"\n Background<\/jats:title>\n Intellectual disability (ID) is a common neurodevelopmental disorder affecting 1\u20133% of the general population. Mutations in more than 10% of all human genes are considered to be involved in this disorder, although the majority of these genes are still unknown.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n We investigated 19 small non-consanguineous families with two to five affected siblings in order to identify pathogenic gene variants in known, novel and potential ID candidate genes. Non-consanguineous families have been largely ignored in gene identification studies as small family size precludes prior mapping of the genetic defect.<\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n Using exome sequencing, we identified pathogenic mutations in three genes, DDHD2<\/jats:italic>, SLC6A8<\/jats:italic>, and SLC9A6<\/jats:italic>, of which the latter two have previously been implicated in X-linked ID phenotypes. In addition, we identified potentially pathogenic mutations in BCORL1<\/jats:italic> on the X-chromosome and in MCM3AP<\/jats:italic>, PTPRT<\/jats:italic>, SYNE1<\/jats:italic>, and ZNF528<\/jats:italic> on autosomes.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We show that potentially pathogenic gene variants can be identified in small, non-consanguineous families with as few as two affected siblings, thus emphasising their value in the identification of syndromic and non-syndromic ID genes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jmedgenet-2013-101644","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T23:24:15Z","timestamp":1381533855000},"page":"802-811","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing"],"prefix":"10.1136","volume":"50","author":[{"given":"Janneke H M","family":"Schuurs-Hoeijmakers","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke T","family":"Vulto-van Silfhout","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Unit of Pediatrics and Medical Genetics, Unit of Neurology, Laboratory of Medical Genetics IRCCS Associazione Oasi Maria Santissima, Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisenka E L M","family":"Vissers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse I G M","family":"van de Vondervoort","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bregje W M","family":"van Bon","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep","family":"de Ligt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gilissen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne Y","family":"Hehir-Kwa","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Neveling","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical 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