Mutations in the p63 gene (TP63) underlie several monogenic malformation syndromes manifesting cleft lip with or without cleft palate (CL/P). We investigated whether p63 mutations also result in non-syndromic CL/P. Specifically, we performed mutation analysis of the 16 exons of the p63 gene for 100 Thai patients with non-syndromic CL/P. In total, 21 variant sites were identified. All were single nucleotide changes, with six in coding regions, including three novel non-synonymous changes: S90L, R313G, and D564H. The R313G was concluded to be pathogenic on the basis of its amino acid change, evolutionary conservation, its occurrence in a functionally important domain, its predicted damaging function, its de novo occurrence, and its absence in 500 control individuals. Our data strongly suggest, for the first time, a causative role of a heterozygous mutation in the p63 gene in non-syndromic CL/P, highlighting the wide phenotypic spectrum of p63 gene mutations.
- AEC, ankyloblepharon-ectodermal dysplasia-clefting syndrome
- CL/P, cleft lip with or without cleft palate
- DB, DNA binding
- EEC, ectrodactyly-ectodermal dysplasia-clefting syndrome
- ESE, exonic splicing enhancer
- RHS, Rapp-Hodgkin syndrome
- SAM, sterile α-motif, SR, serine/arginine-rich
- TA, transactivating
- and TI, transactivation inhibitory
- non-syndromic cleft lip
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