HYPOHIDROTIC ECTODERMAL DYSPLASIA GENE

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The proposed research is part of an on-going collaborative effort to isolate and characterize the X-linked hypohidrotic ectodermal dysplasia (EDA) gene. EDA, an X linked disorder characterized by the congenital absence of hair, teeth, and eccrine sweat glands, is hypothesized to be due to a defect in epithelial-mesenchymal interactions during morphogenesis. Identification of the EDA gene and the mutations within it are of medical significance for the diagnosis and counseling of families with EDA, the most common form of ectodermal dysplasia. Its characterization will assist in our understanding of the biologic mechanisms and pathways, largely unknown, involved in epithelial- mesenchymal reciprocal interactions during differentiation of the epidermal and oral ectoderm. The goal of the project is to isolate candidates genes for the EDA locus by the method of positional cloning.The disorder has been mapped to a 200-300 kb region of the X chromosome (Xq13.1), and genomic clones will be isolated from the EDA critical region by an analysis of patients previously identified with molecular rearrangements. These clones will be screened for expressed sequences, and used to isolate candidate genes from cDNA libraries. The candidate gene will be tested to prove it is truly the EDA gene by the identification of mutations within it by screening >130 unrelated affected individuals. A detailed analysis of the nature and site of mutations within the EDA gene will then be undertaken.