title: ADULT ectodermal dysplasia syndrome resulting from the missense mutation R298Q in the p63 gene.
abstract: Several ectodermal dysplasia syndromes have been shown to result from mutations in the gene that encodes the transcription factor p63. We describe an 11-year-old boy, with clinically normal parents, who had a developmental disorder that resembled EEC (ectrodactyly ectodermal dysplasia-clefting) syndrome (OMIM 604292). He had ectrodactyly and missing middle fingers bilaterally, onychodysplasia, hypodontia with missing teeth, hypohidrosis and lacrimal duct obstruction. DNA sequencing disclosed a heterozygous G-->A substitution at nucleotide 893, that converts an arginine residue (CGA) to glutamine (CAA), the mutation being designated R298Q. This mutation occurs within the DNA-binding domain of p63, and is close to many of the published EEC syndrome mutations. However, R298Q has been described once previously in a large German pedigree, not with EEC syndrome, but another ectodermal dysplasia disorder, ADULT (acro-dermato-ungual-lacrimal-tooth) syndrome (OMIM 103285). Further clinical assessment in our patient revealed that, apart from not having cleft lip and/or palate, he had an exfoliative dermatitis of his hands and feet, and some freckling on his face and shoulders. Collectively, these features support a diagnosis of ADULT syndrome. This study has identified a specific genotype-phenotype correlation in a rare ectodermal dysplasia syndrome and the findings are useful in improving genetic counselling in this family.
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's, and St Thomas' School of Medicine, St Thomas' Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Chan
authors.forename: J I
authors.initials: JI
authors.lastname: Harper
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D001483:Base Sequence; D002648:Child; D004268:DNA-Binding Proteins; D004476:Ectodermal Dysplasia / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006226:Hand Deformities / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000235:genetics*; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins