Leoyklang P, Siriwan P, Shotelersuk V
J Med Genet. 2006 Jun;43(6):e28. doi: 10.1136/jmg.2005.036442.
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.
p63基因（TP63）的突变是几种单基因畸形综合征的基础，这些综合征表现为伴有或不伴有腭裂的唇裂（CL/P）。我们研究了p63突变是否也会导致非综合征性CL/P。具体而言，我们对100名患有非综合征性CL/P的泰国患者的p63基因的16个外显子进行了突变分析。总共鉴定出21个变异位点。所有变异均为单核苷酸变化，其中6个位于编码区，包括3个新的非同义变化：S90L、R313G和D564H。基于R313G的氨基酸变化、进化保守性、其在功能重要结构域中的出现情况、其预测的有害功能、其新生性以及在500名对照个体中的缺失，得出该突变具有致病性的结论。我们的数据首次有力地表明，p63基因杂合突变在非综合征性CL/P中具有致病作用，突出了p63基因突变广泛的表型谱。
