Improved definition of carrier status in X-linked hypohidrotic ectodermal dysplasia by use of restriction fragment length polymorphism-based linkage analysis.

The detection of carriers of the X-linked disorder hypohidrotic ectodermal dysplasia is problematic because of random X-inactivation; the diagnosis was previously based on the observation of subtle defects in ectodermal structures in at-risk females. Linkage studies have recently mapped hypohidrotic ectodermal dysplasia to the region Xq11-q21.1. We assessed the improvement in carrier detection by the method of linkage analysis, in which restriction fragment length polymorphisms were used as markers, in 72 at-risk female members of 29 families. Carriers analyses were based on pedigree information, dental examination of at-risk females (phenotype), and DNA analyses at seven linked marker loci. Linkage analysis based on restriction fragment length polymorphisms significantly improved risk estimates over those based on phenotype and pedigree alone. When all available information was combined, 85% (61/72) of the at-risk females had final risks of less than 5% or greater than 95%, and 68% (49/72) had risks less than 1% or greater than 99%. A diagnosis of hypohidrotic ectodermal dysplasia was also excluded (97.5% probability) by DNA and linkage analyses from a sample of cord blood from an at-risk male; a similar approach can be taken for prenatal diagnosis of the disorder.