title: Rapp-Hodgkin syndrome and the tail of p63.
abstract: We report the clinical and molecular abnormalities in a 19-year-old woman with Rapp-Hodgkin ectodermal dysplasia syndrome. The physical features include mid-facial hypoplasia, uncombable hair, cleft palate and bifid uvula, lacrimal duct obstruction and dry skin. Sequencing of the p63 gene reveals a new heterozygous frameshift mutation, 1787delG, in exon 14. The frameshift results in changes to the tail of p63 with the addition of 68 missense amino acids downstream and a delayed termination codon that extends the protein length by 21 amino acids. These changes are predicted to disrupt the normal repressive function of the transactivation inhibitory domain leading to gain-of-function for at least two isoforms of the p63 transcription factor. The expanding p63 mutation database demonstrates that there is overlap between Rapp-Hodgkin syndrome and several other ectodermal dysplasia syndromes, notably Hay-Wells syndrome, and that characterization of the functional consequences of these p63 gene mutations at a molecular and cellular level is likely to provide further insight into the clinical spectrum of these developmental malformation syndromes.
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Chan
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: S
authors.initials: S
authors.lastname: Kivirikko
mesh_terms: D000328:Adult; D001483:Base Sequence; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005147:Facial Bones / Q000002:abnormalities; D019066:Facies; D005260:Female; D016158:Genes, p53; D006197:Hair / Q000002:abnormalities; D006801:Humans; D009154:Mutation; D013577:Syndrome