A novel mutation in the TP63 gene

Cleft lip with or without cleft palate (CL/P) is the most common craniofacial anomaly with a high incidence of live births. The specific pathogenesis of CL/P is still unclear, although plenty of studies have been conducted. Variations of tumor protein 63 (TP63) was reported to be related to the phenotype of CL/P. A Chinese pedigree with CL/P was collected. The proband is a 3-year-old boy with the phenotype of CL/P, while his development and intelligence are normal. The proband's uncle and grandmother both have the phenotype of cleft lip and cleft palate. Cytogenetic analysis and chromosomal microarray analysis (CMA) were performed, followed by whole exome sequencing (WES) and sanger validation. Analysis of WES revealed a variant of C>T at nucleotide position 1324 (1324C>T) of TP63 gene, possibly producing a truncated protein with a premature stop codon at amino acid position 442 (p.Q442*). This mutation was localized at the oligomerization domain (OD) of TP63 and might impair the capacity of p63 oligomerization. This c.1324C>T (p.Q442*) mutation of TP63 was not reported in literature before and also not found in NCBI dbSNP, genome AD, ExAC, and 1000 human genome dataset. Confirmation of Sanger sequencing was consistent with that of the WES. In summary, this mutation can be interpreted as Likely Pathogenic according to ACMG guidelines.