Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in theTP63Gene

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.

P63‐related disorders: Dermatological characteristics in 22 patients

“…Moreover, all RHS mutations overlap with AEC mutations in the SAM or TI domains of TP63 . RHS represents a mild form of AEC syndrome …”

“…RHS represents a mild form of AEC syndrome. [12][13][14][15][16][17][18][19][20] Only four female patients presented with isolated ectodermal dysplasia Note : Patient 8 presented with clefting and genitourinary manifestations, that is urethral stenosis, painful urination and chronic haematuria. He was classified as EEC.…”