Association and mutation analyses of the irf6 gene in families with nonsyndromic and syndromic cleft lip and/or cleft palate

Abstract

Objectives: (1) To detect interferon regulatory factor 6 gene (IRF6) mutations in newly recruited Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) families. (2) To test for association, in nonsyndromic cleft lip and/or cleft palate (NSCL/P) and in VWS/PPS families, the single nucleotide polymorphism (SNP) rs642961, from the IRF6 enhancer AP-2a region, alone or as haplotype with rs2235371, a coding SNP (Val274Ile). Design: IRF6 mutation screening was performed by direct sequencing and genotyping of rs642961 and rs2235371 by TaqMan technology. Patients: Seventy-one Swedish NSCL/P families, 24 Finnish cleft palate (CP) families, and 24 VWS/PPS families (seven newly recruited) were studied. Results: Allelic and genotypic frequencies in each phenotype were compared to those of the controls, and no significant difference could be observed. IRF6 gene mutation was detected in six of the seven new VWS/PPS families. Association analysis of the entire VWS/PPS sample set revealed the A allele from rs642961 to be a risk allele. Significant association was detected in the Swedish CP subset of our NSCL/P collection where the G-C haplotype for rs642961-rs2235371 were at risk (P = .013). Conclusions: Our resultsdonot support thepreviouslyreportedassociationbetweentheAallele of rs642961 and theNSCLphenotype.However, in the VWS/PPS families, theAallelewas a risk allele and was, in a large majority (.80%), transmitted on the same chromosome as the IRF6 mutation. © Copyright 2014 American Cleft Palate-Craniofacial Association.