Mutations in the TP63 gene encoding the transcription factor p63 result in various ectodermal dysplasia syndromes. Most cases with TP63 mutations show cleft lip/palate regardless of the position of the mutations and there is a clear genotype-phenotype correlation. Of these, mutations in the sterile alpha motif (SAM) domain of p63 are known to underlie ankyloblepharon, ectodermal defects and cleft lip/palate (AEC) syndrome (OMIM: 106260) or Rapp-Hodgkin syndrome (OMIM: 129400). The patients of these diseases did not have ectorodactyly or syndactyly. We herein report a mild ectodermal dysplasia with a novel heterozygous mutation in the SAM domain of p63.
A 3-year-old Lebanese girl had various symptoms including atrophic scarring hair loss, wiry hair, oligodontia, nail dystrophies, a thin upper lip with prominent columella and a smooth tongue surface. However, she did not show cleft lip/palate, lacrimal duct problems, ectrodactyly, syndactyly or ankyloblepharon. Her parents didn’t show any ectodermal abnormalities.  
Direct sequencing analyses revealed that the patient had a novel heterozygous missense mutation c.1748A>T (p.Asp583Val) in exon14 of the TP63 gene. In overexpressed cultured cells, expression of mutant (Mut) p63 protein was markedly reduced compared with the wild-type (Wt) p63 protein. Luciferase activity was found to be significantly suppressed in the presence of the Mut compared with Wt. 
The patient had mild ectodermal dysplasia phenotype with mutation in the SAM domain of p63 which is rare. Our results provide crucial information to better understand the molecular basis of phenotypic heterogeneity in ectodermal dysplasia with TP63 gene.

A mutation in the SAM domain of p63 causing a mild ectodermal dysplasia phenotype