827 Elucidation of the pathogenesis for a mild form of ectodermal dysplasia caused by a TP63 gene mutation

TP63 gene encodes p63, which is a major transcription factor of the epithelial system. Mutations in underlie variety autosomal dominantly-inherited ectodermal dysplasia syndromes, which, most cases, share several symptoms including cleft lip/palate. In this study, we analyzed child with certain showing hypotrichosis, oligodontia, and hypoplastic nails, but did not have We identified novel heterozygous missense mutation c.1798G>T (p.G600C) SAM domain patient. Notably, other mutations codon 600, p.G600D p.G600V, caused dysplasia, phenotypes were more severe than those present case. As next step, order to clarify effect p.G600C found our patient two previously reported on expression function performed western blots an overexpression system cultured cells. The results showed changes pattern wild-type protein condition that each mutant p63 co-transfected. similar system, also conducted luciferase reporter assays using promoter CDH3, bona-fide target p63. that, as compared only was expressed, activity significantly reduced when expressed alone or proteins co-expressed. addition, less effective inhibiting p63-induced proteins, suggesting possibility there difference degree dominant-negative among might affect determining phenotypic severity.