IRF6 mutation screening in non-syndromic orofacial clefting: analysis of 1521 families.
Van der Woude syndrome (VWS) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC) and lower lip pits. The clinical presentation of VWS is variable and can present as an isolated OFC, making it difficult to distinguish VWS cases from individuals with non-syndromic OFCs. About 70% of causal VWS mutations occur in IRF6, a gene that is also associated with non-syndromic OFCs. Screening for IRF6 mutations in apparently non-syndromic cases has been performed in several modestly sized cohorts with mixed results. In this study, we screened 1521 trios with presumed non-syndromic OFCs to determine the frequency of causal IRF6 mutations. We identified seven likely causal IRF6 mutations, although a posteriori review identified two misdiagnosed VWS families based on the presence of lip pits. We found no evidence for association between rare IRF6 polymorphisms and non-syndromic OFCs. We combined our results with other similar studies (totaling 2472 families) and conclude that causal IRF6 mutations are found in 0.24-0.44% of apparently non-syndromic OFC families. We suggest that clinical mutation screening for IRF6 be considered for certain family patterns such as families with mixed types of OFCs and/or autosomal dominant transmission.
['Leslie|E J|EJ|', 'Koboldt|D C|DC|', 'Kang|C J|CJ|', 'Ma|L|L|', 'Hecht|J T|JT|', 'Wehby|G L|GL|', 'Christensen|K|K|', 'Czeizel|A E|AE|', 'Deleyiannis|F W-B|FW|', 'Fulton|R S|RS|', 'Wilson|R K|RK|', 'Beaty|T H|TH|', 'Schutte|B C|BC|', 'Murray|J C|JC|', 'Marazita|M L|ML|']
D000015:Abnormalities, Multiple D000328:Adult D044466:Asians D001921:Brain D002648:Child D002971:Cleft Lip D002972:Cleft Palate D003560:Cysts D004252:DNA Mutational Analysis D003937:Diagnosis, Differential D005260:Female D015870:Gene Expression D005820:Genetic Testing D055106:Genome-Wide Association Study D005838:Genotype D006801:Humans D050835:Interferon Regulatory Factors D008046:Lip D008297:Male D009154:Mutation D010375:Pedigree D010641:Phenotype D044465:Whites
mutation screening interferon regulatory factor 6 non-syndromic oral clefts syndromic cleft