The EDAR370A allele attenuates the severity of hypohidrotic ectodermal dysplasia caused by EDA gene mutation

摘要

Madam, Anhidrotic or hypohidrotic ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising hypotrichosis, hypodontia and hypo/anhidrosis. The most frequent form of HED/EDA results from mutations in the EDA (formerly EDA1) gene (chromosome Xq12-q13.1) encoding ectodysplasin. Mutations in the EDA receptor (EDAR, chromosome 2q13) and in the EDAR-associated death domain EDARADD (chromosome 1q42-q43) have been shown to cause autosomal recessive and dominant HED forms, respectively. These three forms are clinically indistinguishable, probably because they alter a single signal transduction pathway. Indeed, the binding of ectodysplasin to its receptor, EDAR, allows the recruitment of EDARADD as an adapter to activate the NF-kB signalling pathway. This pathway is necessary for initiation, formation and differentiation of skin appendages. Both inter- and intrafamilial clinical heterogeneity have been described in X-linked HED, suggesting that additional genetic factors may influence the severity of this condition.