{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:58:15Z","timestamp":1767833895384,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,6]],"date-time":"2015-01-06T00:00:00Z","timestamp":1420502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000871","name":"Newlife Foundation for Disabled Children","doi-asserted-by":"publisher","award":["SG\/12-13\/07"],"award-info":[{"award-number":["SG\/12-13\/07"]}],"id":[{"id":"10.13039\/501100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>Individuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and\/or palate, were exome\u2010sequenced. In each case, sequencing revealed the underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype and phenotype relationships. These include the molecular diagnosis of an individual with Nager syndrome and a family exhibiting an atypical incontinentia pigmenti phenotype with a missense mutation in <jats:italic><jats:styled-content style=\"fixed-case\">IKBKG<\/jats:styled-content><\/jats:italic>. <jats:italic><jats:styled-content style=\"fixed-case\">IKBKG<\/jats:styled-content><\/jats:italic> mutations are typically associated with preterm male death, but this variant is associated with survival for 8\u201315\u2009days. The third family exhibits unusual phenotypic features and the proband received a provisional diagnosis of Pierre Robin sequence (<jats:styled-content style=\"fixed-case\">PRS<\/jats:styled-content>). Affected individuals share a novel deleterious mutation in <jats:italic><jats:styled-content style=\"fixed-case\">IRF6<\/jats:styled-content><\/jats:italic>. Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">IRF6<\/jats:styled-content><\/jats:italic> cause Van der Woude and popliteal pterygium syndrome and contribute to nonsyndromic cleft lip phenotypes but have not previously been associated with a <jats:styled-content style=\"fixed-case\">PRS<\/jats:styled-content> phenotype. Exome sequencing followed by <jats:italic>in silico<\/jats:italic> screening to identify candidate causal variant(s), and functional assay in some cases offers a powerful route to establishing molecular diagnoses. This approach is invaluable for conditions showing phenotypic and\/or genetic heterogeneity including cleft lip and\/or palate phenotypes where many underlying causal genes have not been identified.<\/jats:p>","DOI":"10.1111\/cge.12547","type":"journal-article","created":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T17:33:29Z","timestamp":1417455209000},"page":"441-449","source":"Crossref","is-referenced-by-count":15,"title":["Resolving clinical diagnoses for syndromic cleft lip and\/or palate phenotypes using whole\u2010exome sequencing"],"prefix":"10.1111","volume":"88","author":[{"given":"R.J.","family":"Pengelly","sequence":"first","affiliation":[{"name":"Genetic Epidemiology and Genomic Informatics, Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Upstill\u2010Goddard","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology and Genomic Informatics, Faculty of Medicine 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