A mutation of the p63 gene in non-syndromic cleft lip.
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.
Leoyklang
P
P
Siriwan
P
P
Shotelersuk
V
V
D002675:Child, Preschool; D002971:Cleft Lip / Q000175:diagnosis* / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D017354:Point Mutation; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins