{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:06:27Z","timestamp":1782781587995,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T00:00:00Z","timestamp":1348444800000},"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:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Nonsyndromic cleft lip with or without cleft palate (NSCL\/P) is a common birth defect with complex etiology reflecting the action of multiple genetic and environmental factors. Genome\u2010wide association studies have successfully identified five novel loci associated with NSCL\/P, including a locus on 1p22.1 near the <jats:italic>ABCA4<\/jats:italic> gene. Because neither expression analysis nor mutation screening support a role for <jats:italic>ABCA4<\/jats:italic> in NSCL\/P, we investigated the adjacent gene <jats:italic>ARHGAP29<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Mutation screening for <jats:italic>ARHGAP29<\/jats:italic> protein coding exons was conducted in 180 individuals with NSCL\/P and controls from the United States and the Philippines. Nine exons with variants in <jats:italic>ARHGAP29<\/jats:italic> were then screened in an independent set of 872 cases and 802 controls. <jats:italic>Arhgap29<\/jats:italic> expression was evaluated using in situ hybridization in murine embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Sequencing of <jats:italic>ARHGAP29<\/jats:italic> revealed eight potentially deleterious variants in cases including a frameshift and a nonsense variant. <jats:italic>Arhgap29<\/jats:italic> showed craniofacial expression and was reduced in a mouse deficient for <jats:italic>Irf6<\/jats:italic>, a gene previously shown to have a critical role in craniofacial development.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The combination of genome\u2010wide association, rare coding sequence variants, craniofacial specific expression, and interactions with <jats:italic>IRF6<\/jats:italic> support a role for <jats:italic>ARHGAP29<\/jats:italic> in NSCL\/P and as the etiologic gene at the 1p22 genome\u2010wide association study locus for NSCL\/P. This work suggests a novel pathway in which the <jats:italic>IRF6<\/jats:italic> gene regulatory network interacts with the Rho pathway via <jats:italic>ARHGAP29<\/jats:italic>. Birth Defects Research (Part A) 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23076","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T11:59:08Z","timestamp":1348487948000},"page":"934-942","source":"Crossref","is-referenced-by-count":88,"title":["Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome\u2010wide association on chromosome 1p22"],"prefix":"10.1002","volume":"94","author":[{"given":"Elizabeth J.","family":"Leslie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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