FOXE1 mutations in Thai patients with oral clefts

Summary Non-syndromic oral clefts comprising cleft lip with and without cleft palate (CL/P) and cleft palate only (CPO) are common birth defects worldwide. Their aetiology involves both environmental and genetic factors. FOXE1 has previously been reported to be associated with oral clefts in some populations. Here, we investigate whether mutations in FOXE1 play a part in the formation of oral cleft in a Thai population. We first performed PCR-RFLP to genotype a previously reported associated polymorphism, c.-1204C > G (rs111846096), in our cohort. No association was found. In addition, two unrelated unaffected controls were found to be homozygous GG, indicating that homozygous GG at this c.-1204 position was not sufficient for the development of oral clefts. We then sequenced the entire coding region of FOXE1 in 458 unrelated individuals (146 CPOs, 108 CL/Ps and 204 Thai controls). Five different non-synonymous variants, c.274G > T (p.D92Y), c.569C > G (p.P190R), c.569C > T (p.P190L), c.664C > T (p.R222C) and c.1090G > A (p.G364S), were identified in CPOs and one, c.572C > G (p.P191R), in CL/P. All these six variants were in heterozygous state, each identified in one patient, and absent in 204 controls. Except the p.P190R, which was previously reported, the other five variants were novel. Our study identifies probable susceptibility variants of FOXE1 for oral clefts in the Thai population.