Abstract: Objectives: Cleft lip and/or palate (CL/P) is the most common craniofacial congenital disease, with a complex aetiology. This study aimed to identify the causative gene mutation of a Han Chinese family with CL/P. Methods: Whole exome sequencing was conducted on the proband and hisfparnets. A Mendelian dominant inheritance model, allele frequency, mutationtypes and literature review were used to screen and filter the variants. The candidate was validated by Sanger sequencing. Conservation analysis was conducted.Results: A heterozygous missense mutation c.2294G>A in the Intraflagellar transport 88 (IFT88) gene predicting p.Arg750Lys was identified. Minor allele frequency of the mutation was low. Sanger sequencing verified the variant and the dominant inheritance model in the family. The missense alteration affects an amino acid that is evolutionarily conserved in the IFT88 protein. Conclusions: Our findings suggest that c.2294G>A in IFT88 may be the causative mutation of this pedigree. Our results add to the evidence that IFT88 variants play a role in the pathogenesis of orofacial clefts.

Key words: non-syndromic cleft lip and/or palate, IFT88, whole exome sequencing