A novel splicing mutation of ectodysplasin A gene responsible for hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is characterized by hypohidrosis, hypodontia, sparse hair, and characteristic facial features. This condition is caused by an ectodysplasin A (EDA) gene mutation. In this study, we examined two HED pedigrees and investigated the molecular genetics of the defect. Direct sequencing analysis revealed a previously unidentified mutation in the EDA splice donor site (c.526 + 1G>A). The function of the mutant EDA gene was predicted through online investigations and subsequently confirmed by splicing analysis in vitro. The mutation resulted in the production of a truncated EDA-A1 protein caused by complete omission of exon 3. This novel functional skipping-splicing EDA mutation was considered to be the cause of HED in the two pedigrees reported here. Our findings, combined with those reported elsewhere, provide an improved understanding of the pathogenic mechanism of HED as well as important information for a genetic diagnosis.