A novel large deletion that encompasses EDA and the downstream gene AWAT2 causes X-linked hypohidrotic/anhidrotic ectodermal dysplasia

Chaudhary, Ajay Kumar; Sankar, V.H.; Bashyam, Murali D.

doi:10.1016/j.jdermsci.2016.06.012

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…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

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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

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“…The novel mutation c.354T>G was predicted to be decayed by NMD or truncate a major part of the protein. It is a loss-of-function mutation [ 35 , 36 ]. Interestingly, the most prevalent mutation c.321C>A (p.Cys107*) and c.682T>A (p.Phe228Ile) did not show up in our study.…”

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

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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.

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“…The study was carried out on 29 unrelated XLHED families including 17 new (Table 2) and 12 from our previous studies (Table 3) (Bashyam, Chaudhary, Reddy, et al, 2012; Chaudhary et al, 2016; RamaDevi et al, 2008). In all, we performed molecular genetic screening on a total of 73 individuals (including 31 affected male patients and 42 additional members) and six chorionic villi samples (CVS).…”

Section: Resultsmentioning

confidence: 99%

“…We had earlier commenced molecular genetic characterization of disease‐causing pathogenic variants in HED families from India including 12 XLHED families (Bashyam, Chaudhary, Reddy, et al, 2012; Chaudhary et al, 2016; RamaDevi et al, 2008). In the present study, we evaluated 17 new suspected XLHED families in which the proband's age ranged from 20 days to 32 years (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Ectodysplasin pathogenic variants affecting the furin‐cleavage site and unusual clinical features define X‐linked hypohidrotic ectodermal dysplasia in India

Chaudhary

Gholse

Nagarajaram

et al. 2021

American J of Med Genetics Pt A

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Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by mutational inactivation of a developmental pathway responsible for generation of tissues of ectodermal origin. The X-linked form accounts for the majority of HED cases and is caused by Ectodysplasin (EDA) pathogenic variants. We performed a combined analysis of 29 X-linked hypohidrotic ectodermal dysplasia (XLHED) families (including 12 from our previous studies). In addition to the classical triad of symptoms including loss (or reduction) of ectodermal structures, such as hair, teeth, and sweat glands, we detected additional HED-related clinical features including facial dysmorphism and hyperpigmentation in several patients. Interestingly, global developmental delay was identified as an unusual clinical symptom in many patients. More importantly, we identified 22 causal pathogenic variants that included 15 missense, four small in-dels, and one nonsense, splice site, and large deletion each. Interestingly, we detected 12 unique (India-specific) pathogenic variants. Of the 29 XLHED families analyzed, 11 (38%) harbored pathogenic variant localized to the furin cleavage site. A comparison with HGMD revealed significant differences in the frequency of missense pathogenic variants; involvement of specific exons and/or protein domains and transition/ transversion ratios. A significantly higher proportion of missense pathogenic variants

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A novel large deletion that encompasses EDA and the downstream gene AWAT2 causes X-linked hypohidrotic/anhidrotic ectodermal dysplasia

Cited by 7 publications

References 9 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

Ectodysplasin pathogenic variants affecting the furin‐cleavage site and unusual clinical features define X‐linked hypohidrotic ectodermal dysplasia in India

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