Abstract
X‐linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by severe hypohidrosis, hypotrichosis, and hypodontia. The gene responsible for this pleiotropic syndrome (ED1) consists of 12 exons, 8 of them coding for a transmembrane protein (ectodysplasin‐A; EDA‐A) involved in the developmental process of epithelial–mesenchymal interaction. ED1 mutations that cause alterations in this protein lead to the XLHED phenotype. The major objective of the present study was to detect ED1 mutations in four Brazilian families with the XLHED phenotype and to compare them to the more than 60 different mutations already reported. DNA of the EDA‐A coding exons was amplified by PCR, and single strand conformation analysis (SSCA) of the electrophoretic bands was carried out in polyacrylamide gel stained with silver nitrate. Two of these four families showed altered DNA band patterns. Subsequent DNA sequencing of the two mutated exons showed: (1) a 36 nucleotide deletion at exon 5 responsible for the loss of four Gly‐X‐Y repeats of the collagen subdomain of EDA‐A; (2) a guanine deletion at exon 6 (966 or 967 sites) that alters EDA‐A after amino acid 241 and leads to a premature ending at amino acid 279. This mutation at exon 6 seems not to have been reported previously and determines a truncated EDA‐A without a part of its extracellular domain that contains the whole TNF homologue subdomain. These two DNA mutations are compatible with the XLHED phenotype. In the other two families the PCR–SSCA methodology was unable to detect any mutation responsible for the XLHED phenotype. © 2003 Wiley‐Liss, Inc.