{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:28:54Z","timestamp":1776371334928,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,18]],"date-time":"2012-10-18T00:00:00Z","timestamp":1350518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND<\/jats:bold>: Nonsyndromic cleft lip with or without cleft palate (NSCL\/P) is one of the most common of all congenital anomalies, and has a multifactorial etiology involving both environmental and genetic factors. Recent genome\u2010wide association studies (GWAS) identified strong association between a locus on chromosome 10q25.3 and NSCL\/P in European samples. One gene at 10q25.3, the ventral anterior homeobox 1 (<jats:italic>VAX1<\/jats:italic>) gene, is considered a strong candidate gene for craniofacial malformations. The purpose of the present study was to provide further evidence that <jats:italic>VAX1<\/jats:italic> is the causal gene at the 10q25.3 locus through identification of an excess of rare mutations in patients with NSCL\/P. <jats:bold>METHODS<\/jats:bold>: The 5\u2032UTR, complete coding regions, and adjacent splice sites of the two known <jats:italic>VAX1<\/jats:italic> isoforms were sequenced in 384 patients with NSCL\/P and 384 controls of Central European descent. Observed variants were investigated with respect to familial cosegregation or de novo occurrence, and in silico analyses were performed to identify putative effects on the transcript or protein level. <jats:bold>RESULTS<\/jats:bold>: Eighteen single\u2010base variants were found, 15 of them rare and previously unreported. In the long <jats:italic>VAX1<\/jats:italic> isoform, predicted functionally relevant variants were observed more often in NSCL\/P cases, although this difference was not significant (<jats:italic>p<\/jats:italic> = 0.17). Analysis of family members demonstrated incomplete cosegregation in most pedigrees. <jats:bold>CONCLUSION<\/jats:bold>: Our data do not support the hypothesis that highly penetrant rare variants in <jats:italic>VAX1<\/jats:italic> are a cause of NSCL\/P. To determine whether <jats:italic>VAX1<\/jats:italic> is the causative gene at 10q25.3 further research, in particular into the biologic function of its long isoform, is warranted. Birth Defects Research (Part A), 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bdra.23078","type":"journal-article","created":{"date-parts":[[2012,10,18]],"date-time":"2012-10-18T19:37:13Z","timestamp":1350589033000},"page":"925-933","source":"Crossref","is-referenced-by-count":16,"title":["Resequencing of <i>VAX1<\/i> in patients with nonsyndromic cleft lip with or without cleft palate"],"prefix":"10.1002","volume":"94","author":[{"given":"Entessar","family":"Nasser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Mangold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela 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