X‐linked hypohidrotic ectodermal dysplasia. Genetic and dental findings in 67 Danish patients from 19 families

Abstract

This study aimed to investigate genotype and phenotype in males affected with X-linked hypohidrotic ectodermal dysplasia (HED) and in female carriers, to analyse a possible genotype-phenotype correlation, and to analyse a possible relation between severity of the symptoms and the X-chromosome inactivation pattern in female carriers. The study group comprised 67 patients from 19 families (24 affected males and 43 female carriers). All participants had clinical signs of ectodermal dysplasia and a disease-causing EDA mutation. The EDA gene was screened for mutations by single-stranded conformational polymorphism and direct sequencing. Multiplex ligation-dependent probe amplification (MLPA) analysis was used to detect deletions/duplications in female probands. Sixteen different EDA mutations were detected in the 19 families, nine not described previously. The MLPA analysis detected a deletion of exon 1 in one female proband. No genotype-phenotype correlations were observed, and female carriers did not exhibit a skewed X-chromosome inactivation pattern. However, in two female carriers with pronounced clinical symptoms, in whom the parental origin of each allele was known, we observed that mainly the normal allele was inactivated.

Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia

“…Sequence analysis of the EDA gene in our XLHED cohort revealed a total of 26 different EDA mutations, 11 of which are known from the literature2–4 7 8 17–19 while 15 have not yet been described (tables 1–3). None of the missense or splice site mutations was present in a control group of 100 healthy males.…”

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature

“…For genetic counseling, HED related gene screening is needed. In the literature, Sanger sequencing and multiplex ligation-dependent probe amplification have been commonly used for EDA mutation discovery in both research and clinical studies (Lexner et al, 2008). Recently, whole-exome sequencing has been reported to be an economical and rapid tool for genetic diagnosis, and it has been used to diagnose types of disorders similar to ED (Haghighi et al, 2013).…”

The Second Deletion Mutation in Exon 8 of <b><i>EDA</i></b> Gene in an XLHED Pedigree

“…As a member of the TNF superfamily, the EDA gene expresses in ectodermal tissues and encodes the transmembrane type II protein [11]. The EDA gene undergoes extensive alternative splicing which leads to various isoforms, of which two are mainly functional, EDA-A1 (391 amino acids) and EDA-A2 (389 amino acids).…”