A Novel IRF6 Variant Detected in a Family With Nonsyndromic Cleft Lip and Palate by Whole Exome Sequencing

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common congenital craniofacial malformation, and its harmful effects on affected individuals and families are apparent. The causative genes and their mechanisms are not completely clear, although several studies have been conducted. Accordingly, in the present study, we recruited a Han Chinese family with hereditary NSCL/P to explore the possible causative variants of this disease using whole exome sequencing. Bioinformatics screening and analysis, mutation function prediction, species conservation analysis, and homology protein modeling were used to identify the variants and evaluate their influence. A mutation in the interferon regulatory factor 6 (IRF6) gene (c.961C>T; p.Val321Met) was detected as a candidate causative variant and predicted to be deleterious. The codon was found to be conserved in many species, and the residue change caused by this mutation changed the structure of IRF6 to a certain degree. The findings suggest that this IRF6 variant is probably the pathogenic cause of NSCL/P in this family. Our results further provide evidence that IRF6 variants play a role in the etiology of NSCL/P.