Eight Mutations of Three Genes (EDA, EDAR, and WNT10A) Identified in Seven Hypohidrotic Ectodermal Dysplasia Patients

Abstract

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1–6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient’s total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients.

The biology and genetics of curly hair

“…A second developmental gene associated with hair morphology is WNT10A (wingless‐type MMTV integration site family, member 10A) . WNT10A is upregulated at the beginning of the hair growth cycle and mutations in this gene are known to cause misformed hair and appendage abnormalities in hypohidrotic ectodermal dysplasia patients . However, a known mutation in WNT10A (rs7349332) in combination with mutations in TCHH (rs11803731) and FRAS 1 (rs1268789) form a potential signature for straight hair of potential use in forensics …”

Genetic diagnosis for X‐linked hypohidrotic ectodermal dysplasia family with a novel Ectodysplasin A gene mutation

“…There are 3 subtypes of HED including X‐linked (XLHED, OMIM 305100), autosomal dominant (ADHED, OMIM 129490, or 614940), and autosomal recessive HED (ARHED, OMIM 224900, or 614941) . Ectodysplasin A ( EDA ; Gene ID: 1896) is the candidate gene for XLHED .…”

“…There are 3 subtypes of HED including X‐linked (XLHED, OMIM 305100), autosomal dominant (ADHED, OMIM 129490, or 614940), and autosomal recessive HED (ARHED, OMIM 224900, or 614941) . Ectodysplasin A ( EDA ; Gene ID: 1896) is the candidate gene for XLHED . The pathogenic genes of both ADHED and ARHED are Ectodysplasin A receptor ( EDAR ; Gene ID: 10913) and EDAR‐associated death domain ( EDARADD ; Gene ID: 128178) .…”

“…4,6 The pathogenic genes of both ADHED and ARHED are Ectodysplasin A receptor (EDAR; Gene ID: 10913) and EDAR-associated death domain (EDARADD; Gene ID: 128178). 4 The pathogenic gene of XLHED, Ectodysplasin A (EDA, OMIM 300451) gene located in Xq13.1 and containing 8 exons, 7 encodes a tumor necrosis factor (TNF)-related ligand family type II transmembrane protein consisting of 391 amino acids. Due to its short coding region, Sanger sequencing was usually used in gene diagnosis of XLHED to obtain accurate and economical results, providing reliable experimental data for clinical diagnosis and genetic counseling.…”

A first case report of hypohidrotic ectodermal dysplasia from Oman

“…Hypohidrotic ectodermal dysplasias (HED) are a group of developmental genetic disorders which primarily affect tissues of ectodermal origin such as teeth, skin, hair, nails, mucous membrane, and sweat glands. HEDs are mostly inherited as X‐linked recessive disorders (OMIM: 305 100) as the result of mutations in the ectodysplasin A (EDA) gene . However, HDE can also be inherited in autosomal dominant (OMIM: 129 490) and autosomal recessive manners (OMIM: 224 900) due to mutations in the ectodysplasin A receptor (EDAR) and EDAR‐associated death domain (EDARADD) genes.…”