{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:23:11Z","timestamp":1790439791995,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE025060, HG005925, DE008559, DE009886, DE016930, DE016148, DE014581, DE018993, and DE011931"],"award-info":[{"award-number":["DE025060, HG005925, DE008559, DE009886, DE016930, DE016148, DE014581, DE018993, and DE011931"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Van der Woude syndrome (VWS<\/jats:styled-content>) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC<\/jats:styled-content>) and lower lip pits. The clinical presentation of VWS<\/jats:styled-content> is variable and can present as an isolated OFC<\/jats:styled-content>, making it difficult to distinguish VWS<\/jats:styled-content> cases from individuals with non\u2010syndromic OFCs<\/jats:styled-content>. About 70% of causal VWS<\/jats:styled-content> mutations occur in IRF6<\/jats:styled-content><\/jats:italic>, a gene that is also associated with non\u2010syndromic OFCs<\/jats:styled-content>. Screening for IRF6<\/jats:styled-content><\/jats:italic> mutations in apparently non\u2010syndromic cases has been performed in several modestly sized cohorts with mixed results. In this study, we screened 1521 trios with presumed non\u2010syndromic OFCs<\/jats:styled-content> to determine the frequency of causal IRF6<\/jats:styled-content><\/jats:italic> mutations. We identified seven likely causal IRF6<\/jats:styled-content><\/jats:italic> mutations, although a posteriori<\/jats:italic> review identified two misdiagnosed VWS<\/jats:styled-content> families based on the presence of lip pits. We found no evidence for association between rare IRF6<\/jats:styled-content><\/jats:italic> polymorphisms and non\u2010syndromic OFCs<\/jats:styled-content>. We combined our results with other similar studies (totaling 2472 families) and conclude that causal IRF6<\/jats:styled-content><\/jats:italic> mutations are found in 0.24\u20130.44% of apparently non\u2010syndromic OFC<\/jats:styled-content> families. We suggest that clinical mutation screening for IRF6<\/jats:styled-content><\/jats:italic> be considered for certain family patterns such as families with mixed types of OFCs<\/jats:styled-content> and\/or autosomal dominant transmission.<\/jats:p>","DOI":"10.1111\/cge.12675","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T09:51:51Z","timestamp":1441705911000},"page":"28-34","source":"Crossref","is-referenced-by-count":50,"title":["IRF6<\/i> mutation screening in non\u2010syndromic orofacial clefting: analysis of 1521 families"],"prefix":"10.1111","volume":"90","author":[{"given":"E.J.","family":"Leslie","sequence":"first","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral Biology School of Dental Medicine, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.C.","family":"Koboldt","sequence":"additional","affiliation":[{"name":"The Genome Institute 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