{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:52:49Z","timestamp":1791820369725,"version":"4.3.4"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T00:00:00Z","timestamp":1538697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17ek0109151"],"award-info":[{"award-number":["JP17ek0109151"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>NCOR1 (nuclear receptor corepressor 1) is a transcriptional coregulatory protein that regulates the balance between histone acetylation and histone deacetylation. <jats:italic>NCOR1<\/jats:italic> is listed as one of the 3,230 dose\u2010sensitive genes which very rarely show truncating mutations in the pediatric population without severe diseases, even in a heterozygous state. In a large cohort study of intellectual disability\/autism spectrum disorder, splicing mutations were identified in two individuals, however, the truncating effects of these splicing mutations have not been examined at the transcription level. We describe a 3\u2010year\u2010old girl who had behavior consistent with autism spectrum disorder, a bifid uvula, and early\u2010onset scoliosis. Trio exome analysis showed a de novo heterozygous mutation at the splice donor site in exon 19 of <jats:italic>NCOR1<\/jats:italic>, c.2182 + 1G &gt; T (NM_00190440.1). Reverse transcription polymerase chain reaction assay confirmed that the splicing mutation results in skipping of exon 19, a shift in the reading frame and then to nonsense\u2010mediated mRNA decay. This patient represents the first patient who has had unequivocal documentation of haploinsufficient for the <jats:italic>NCOR1<\/jats:italic> gene. Based on our observations, we conclude that <jats:italic>NCOR1<\/jats:italic> is indeed a human disease\u2010causing gene. We further suggest that bifid uvula, a micro form of cleft palate, may well be causally related to de novo <jats:italic>NCOR1<\/jats:italic> haploinsufficiency, in that a previously reported deletion mapping study of atypical Smith\u2010Magenis syndrome patients with large deletions and cleft palate identified that <jats:italic>NCOR1<\/jats:italic>, the only loss\u2010of\u2010function\u2010intolerant gene within the region, is located in the smallest region of overlap.<\/jats:p>","DOI":"10.1002\/ajmg.a.40354","type":"journal-article","created":{"date-parts":[[2018,10,6]],"date-time":"2018-10-06T09:43:13Z","timestamp":1538818993000},"page":"2466-2469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Haploinsufficiency of <i>NCOR1<\/i> associated with autism spectrum disorder, scoliosis, and abnormal palatogenesis"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-1110","authenticated-orcid":false,"given":"Yuri","family":"Sakaguchi","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-7686","authenticated-orcid":false,"given":"Tomoko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisato","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineko","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-4135","authenticated-orcid":false,"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.048736"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.73702"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3027"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103233"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.05.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4352"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.214023.113"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.82802"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.10.022"},{"key":"e_1_2_8_16_1","first-page":"852","article-title":"Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia. American Journal of Medical Genetics","volume":"170","author":"Takenouchi T.","year":"2016","journal-title":"Part A"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13316"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg120"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.40354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.40354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:15:02Z","timestamp":1694697302000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.40354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,5]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/ajmg.a.40354"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.40354","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,5]]},"assertion":[{"value":"2017-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}