[Identification of pathogenic variant in a Chinese pedigree affected with non-syndromic cleft lip and palate].

Zhang, Mingjie; Huang, Jia; Shi, Feifei; He, Jiahuan; Xiao, Hai; Wu, Dong; Wang, Hongdan; Liu, Hongyan

OBJECTIVE To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.