title: Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.
abstract: Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.
authors.affiliation: a Department of Pediatrics, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.|b The Institute for Research in Military Medicine, Faculty of Medicine , The Hebrew University of Jerusalem , Israel , and IDF Medical Corps.
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
authors.affiliation: a Department of Pediatrics, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.|c Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.|d The Dr. Pinchas Borenstein Talpiot Medical Leadership Program , Sheba Medical Center , Tel-Hashomer , Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Pode-Shakked
authors.affiliation: e Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Goldstein
authors.affiliation: a Department of Pediatrics, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.|c Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Shpirer
authors.affiliation: f Department of Human Genetics , Radboud University Medical Center , Nijmegen , The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.affiliation: c Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.|e Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
mesh_terms: D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Hay–Wells syndrome; Rapp–Hodgkin syndrome; TP63; ankyloblepharon ectodermal defects Cleft lip/palate (AEC) syndrome; ectodermal dysplasia