title: Mutation screening of IRF6 among families with non-syndromic oral clefts and identification of two novel variants: review of the literature.
abstract: Non-syndromic oral clefts share the main clinical features of Van der Woude Syndrome (VWS), with the exception of the lower lip pit. Thus, about 15% of VWS cases are indistinguishable from cases with non-syndromic oral clefts. IRF6 mutations are the major cause of VWS; however, variants in this gene show strong association with non-syndromic oral clefts, with a higher increased risk among cases with cleft lip only (CLO). A total of 39 individuals, including 16 patients with CLO and 23 patients with a family history of cleft, were examined for IRF6 mutations in the present study. Seven variants, including five known (c.-75-4 A>; G, c.-73T>; C, c.459G>; T 5, c.820G>; A, and c.1060 + 37C>; T) and two novel (c.-75-23G>; C and c.1380G>; T), were found. Both novel variants were inherited from non-affected parents and we did not find also in the 120 control chromosomes. In silico analysis revealed that both c.1380G>; T and c.-75-23G>; C variants may disrupts a putative exonic splicing enhancer and intronic splicing binding site for SC35, respectively. Taken together, the presence of deleterious IRF6 variants in patients with non-syndromic oral clefts could be most likely an evidence for VWS. While, IRF6 variants could, at best, contribute to clefting as part of a complex inheritance pattern, with both additional genes and environmental factors having a role.
authors.affiliation: Human Genome Center, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Iman
authors.initials: I
authors.lastname: Salahshourifar
authors.forename: Wan Azman
authors.initials: WA
authors.lastname: Wan Sulaiman
authors.forename: Ahmad Sukari
authors.initials: AS
authors.lastname: Halim
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors