De novo EDA mutations: Variable expression in two Egyptian families

Gaczkowska, Agnieszka; Abdalla, Ebtesam; Dowidar, Karin; Elhady, Ghada M.; Jagodzińśki, Paweł P.; Mostowska, Adrianna

doi:10.1016/j.archoralbio.2016.03.015

Cited by 12 publications

(16 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This mutation found in this study has not been reported in the databases (https://www.ncbi.nlm.nih.gov/clinvar, http://www.hgmd.cf.ac.uk/ac/index.php). The Ectodysplasin‐A protein encoded by EDA gene consists of 391 amino acids and contains 3 structural domains including N‐terminal intracellular domain (1‐41 amino acids), transmembrane domain (42‐62 amino acids), and C‐terminal extracellular domain (63‐391 amino acids). In this family, the c.302_303delCC [p.Pro101HisfsX11] mutation in the proband's EDA gene induced EDA gene frame shift mutation which led to early termination of EDA gene translation because there was a termination codon TAA at the 11th codon behind the mutational site, so only 110 amino acids were translated and the 101‐110 amino acids were also mismatched.…”

Section: Discussionmentioning

confidence: 99%

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

Liu

et al. 2018

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

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

Liu

et al. 2018

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…It is not rare that mutations of the same gene lead to different phenotypes. For example, mutations in the EDA gene are the cause of some XLHED and non-syndromic oligodontia in patients, and the two diseases are considered to be the same disease with different degrees of severity [ 5 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

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

Zeng

Xiao

et al. 2016

Genes

View full text Add to dashboard Cite

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.

show abstract

“…EDA pathogenic variants that underlie non-syndromic or syndromic oligodontia [11] have been described, likely because they alter a single signal transduction pathway. It has been postulated that X-linked hypohidrotic ectodermal dysplasia (XLHED) and EDA-related NSTA are the same disease with different degrees of expressivity [12].…”

Section: Introductionmentioning

confidence: 99%

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

Martínez-Romero

Ballesta-Martínez

López‐González

et al. 2019

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundEctodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000–100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA.Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed.ResultsA total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel.ConclusionsThis is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.

show abstract

De novo EDA mutations: Variable expression in two Egyptian families

Cited by 12 publications

References 49 publications

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

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

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

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

Contact Info

Product

Resources

About