title: A new mutation in TP63 is associated with age-related pathology.
abstract: Increases in the number of allelic malformation syndromes have led to their classification according to their pathogenesis rather than their clinical specific phenotype. TP63 (also known as TP73L) mutations have been identified in several such syndromes characterized by autosomal dominant transmission and various combinations of ectodermal dysplasia, limb malformations and orofacial clefting. TP63 has not yet been implicated in early aging phenotype in humans, even though p63 activates a program of cellular senescence and p63-compromised mice display features of accelerated aging. We report on a family with four affected adult females presenting with Rapp-Hodgkin syndrome (RHS), an autosomal dominant clinical entity that associates anhidrotic ectodermal dysplasia with cleft lip and palate. Features between RHS and EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) have led to the recent identification of mutations in the TP63 gene, located on 3q27, in this condition. Our patients present typical clinical features of RHS, but also ophthalmic anomalies such as corneal dystrophy and premature menopause (around 30 years). The latter findings have never been reported in this condition, and could be secondary to a new TP63 deletion that has been identified in this family.
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France. m-holder@chru-lille.fr
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Dominique
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000506:Alopecia Areata / Q000235:genetics / Q000473:pathology; D000595:Amino Acid Sequence; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008594:Menopause, Premature / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D013577:Syndrome