De novo missense mutation, S541Y, in the p63 gene underlying Rapp-Hodgkin ectodermal dysplasia syndrome.
Rapp-Hodgkin syndrome (RHS) is an autosomal dominant disorder characterized by ectodermal dysplasia and cleft lip/cleft palate. Very recently, mutations in p63 have been identified as a cause of RHS; to date five such mutations have been identified. We describe a Thai girl with RHS. She had short stature, ectodermal dysplasia, epiphora, cleft lip, cleft palate, and normal development. Mutation analysis for the entire coding region of p63 identified a novel and de novo mutation, 1622C--> A (S541Y), in the SAM domain, predicting an abnormal alpha tail of the p63alpha protein isotypes. This observation supports that majority of patients with RHS are caused by mutations affecting the tail of p63alpha, a region that also contains most of the pathogenic mutations in ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome.
Shotelersuk
V
V
Division of Medical Genetics and Metabolism, Department of Pediatrics, Chulalongkorn University, Bangkok 10330, Thailand. vorasuk.s@chula.ac.th
Janklat
S
S
Siriwan
P
P
Tongkobpetch
S
S
D000015:Abnormalities, Multiple / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000235:genetics*; D013577:Syndrome; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins