X‐linked hypohidrotic ectodermal dysplasia mutations in Brazilian families

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.

Repertoire of mouse ectodysplasin-A (EDA-A) isoforms

“…Consistent with these data, truncated EDA-A1 and EDA-A2, which also lacked the amino acids encoded by exon 4 still bound to their specific receptors and activated NF-κB, and truncated EDA-A1 could rescue part of the Tabby phenotype (Yan et al, 2000;Schneider et al, 2001;Koppinen et al, 2001;Gaide and Schneider, 2003). Furthermore, no mutations in exon 4 have been reported to cause human X-linked anhidrotic ectodermal dysplasia patients (Hashiguchi et al, 2003;Visinoni et al, 2003).…”

Müllerian agenesis with hypohidrotic ectodermal dysplasia syndrome

“…Hypohidrotic ectodermal dysplasia is characterized most notably by abnormal sweat glands (hypohidrosis), decreased hair development (hypotrichosis), and abnormal dentition (hypodontic) with cases of X-linked, autosomal dominant, and autosomal recessive heredity (10,11). Hypohidrotic ectodermal dysplasia syndrome accounts for this patient's hypodontia with absent teeth, hypotrichosis of her scalp and pubic hair, abnormal palate angle, and dysmorphic ears.…”

A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia

“…Mutations in EDA are known to cause ectodermal dysplasia (OMIM 305100), a clinical condition characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). More than 64 mutations in the EDA gene have been identified in association with ED (Visinoni et al 2003), but EDA is rarely reported as being implicated in isolated tooth agenesis (Tao et al 2006;Tarpey et al 2007). The EDA is a type II transmembrane protein containing a small N-terminal intracellular part and a larger C-terminal extracellular part.…”

“…Chromatograms were analyzed using Sequencher v.4.1.2 (Gene Codes Corporation). Primers and sequencing conditions have been described previously (Visinoni et al 2003). Informed consent was obtained from all individuals who participated in this study.…”