{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:06:36Z","timestamp":1782781596155,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T00:00:00Z","timestamp":1469491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["402425\/2014\u20106"],"award-info":[{"award-number":["402425\/2014\u20106"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["457643\/2014\u20105"],"award-info":[{"award-number":["457643\/2014\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/08028\u20101"],"award-info":[{"award-number":["2013\/08028\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,5]]},"abstract":"Non\u2010syndromic cleft lip with or without cleft palate (NSCL<\/jats:styled-content>\/P) is a prevalent, complex congenital malformation. Genome\u2010wide association studies (GWAS<\/jats:styled-content>) on NSCL<\/jats:styled-content>\/P have consistently identified association for the 1p22 region, in which\u2009ARHGAP29<\/jats:styled-content><\/jats:italic> has emerged as the main candidate gene. ARHGAP29<\/jats:styled-content><\/jats:italic> re\u2010sequencing studies in NSCL<\/jats:styled-content>\/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29<\/jats:styled-content><\/jats:italic>, including five missense, one in\u2010frame deletion, and four loss\u2010of\u2010function (LoF<\/jats:styled-content>) variants, in a cohort of 188 familial NSCL<\/jats:styled-content>\/P<\/jats:styled-content> cases. A significant mutational burden was found for LoF<\/jats:styled-content> (Sequence Kernel Association Test, p\u2009=\u20090.0005) but not for missense variants in\u2009ARHGAP29<\/jats:styled-content><\/jats:italic>, suggesting that only LoF<\/jats:styled-content> variants contribute to the etiology of NSCL<\/jats:styled-content>\/P. Penetrance was estimated as 59%, indicating that heterozygous LoF<\/jats:styled-content> variants in ARHGAP29<\/jats:styled-content><\/jats:italic> confer a moderate risk to NSCL<\/jats:styled-content>\/P. The GWAS<\/jats:styled-content> hits in\u2009IRF6<\/jats:styled-content><\/jats:italic> (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co\u2010segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29<\/jats:styled-content><\/jats:italic> represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.<\/jats:p>","DOI":"10.1111\/cge.12823","type":"journal-article","created":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T08:52:42Z","timestamp":1467103962000},"page":"683-689","source":"Crossref","is-referenced-by-count":33,"title":["Impact of rare variants in ARHGAP29<\/scp><\/i> to the etiology of oral clefts: role of loss\u2010of\u2010function vs<\/i> missense variants"],"prefix":"10.1111","volume":"91","author":[{"given":"C.P.","family":"Savastano","sequence":"first","affiliation":[{"name":"Centro de Pesquisa sobre o Genoma Humano e C\u00e9lulas\u2010Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo S\u00e3o Paulo 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