Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair, and teeth. The X-linked form of the disease, caused by mutations in the ED1 gene, represents the majority of HED cases. Autosomal-dominant and -recessive forms occur occasionally and result from mutations in at least two genes: EDAR and EDARADD. These different forms are phenotypically indistinguishable. To better assess the implication of the EDAR gene in HED, we screened for mutations in 37 unrelated HED families or sporadic cases with no detected mutations in the ED1 gene. We identified 11 different mutations, nine of which are novel variants, in two familial and seven sporadic cases. Seven of the 11 are recessive mutations (c.140G>A (p.Cys47Tyr), c.266G>A (p.Arg89His), c.329A>C (p.Asp110Ala), c.442T>C (p.Cys148Arg), c.1208C>T (p.Thr403Met), c.1302G>T (p.Trp434Cys) and c.528+1G>A), and the other four are probably dominant (c.1129C>T (p.Leu377Phe), c.1237A>C (p.Thr413Pro), c.1253T>C (p.Ile418Thr), and c.1259G>A (p.Arg420Gln)). Our study demonstrates that EDAR is implicated in about 25% of non-ED1 HED, and may account for both autosomal-dominant and -recessive forms. The correlation between the nature and location of EDAR mutations and their mode of inheritance is discussed. A genotype-phenotype relationship was evaluated, since such data could be helpful for genetic counseling.