Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia

Abstract Background Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (EDA) gene mutation. Fetus with genetic deficiency of EDA can be prenatally corrected. This study aimed at revealing the pathogenesis of two HED families and making a prenatal diagnosis for one pregnant f...

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Autores principales:	Kang Yu, Yihan Shen, Cai‐Ling Jiang, Wei Huang, Feng Wang, Yi‐Qun Wu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	ectodysplasin A hypohidrotic ectodermal dysplasia novel mutation prenatal diagnosis whole exome sequencing Genetics QH426-470
Acceso en línea:	https://doaj.org/article/123e024150934c0598559367208389b9
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spelling	oai:doaj.org-article:123e024150934c0598559367208389b92021-11-21T19:38:53ZTwo novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia2324-926910.1002/mgg3.1824https://doaj.org/article/123e024150934c0598559367208389b92021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1824https://doaj.org/toc/2324-9269Abstract Background Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (EDA) gene mutation. Fetus with genetic deficiency of EDA can be prenatally corrected. This study aimed at revealing the pathogenesis of two HED families and making a prenatal diagnosis for one pregnant female carrier. Designs Genomic DNA was extracted from two HED patients and sequenced using whole exome sequencing (WES). The detected mutations were confirmed in patients and family members using Sanger sequencing. The expression of soluble ectodysplasin A1 (EDA1) protein was studied by western blot. The transcriptional activity of NF‐κB pathway was tested by dual luciferase assay. The genomic DNA of fetus was extracted from shed chorion cells and EDA gene was screened through Sanger sequencing. Results We identified two novel EDA mutations: c.1136T>C (p.Phe379Ser) and c.[866G>C;868A>T] (p.[Arg289Pro;Ser290Cys]). Further examinations revealed that these two mutated EDA1 proteins showed completely impaired solubility, and the transcriptional NF‐κB activation induced by these missense mutant‐type EDA1 proteins was significantly reduced compared with wild‐type EDA1. Furthermore, the analysis of amniotic fluid samples from a pregnant heterozygote indicated that the fetus was a c.1136T>C mutation female carrier. Conclusions This study extended the mutation spectrum of X‐linked hypohidrotic ectodermal dysplasia (XLHED) and applied prenatal diagnosis for the pregnant carrier, which can be helpful in genetic counseling, prenatal diagnosis, and intervention for the XLHED family.Kang YuYihan ShenCai‐Ling JiangWei HuangFeng WangYi‐Qun WuWileyarticleectodysplasin Ahypohidrotic ectodermal dysplasianovel mutationprenatal diagnosiswhole exome sequencingGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ectodysplasin A hypohidrotic ectodermal dysplasia novel mutation prenatal diagnosis whole exome sequencing Genetics QH426-470
spellingShingle	ectodysplasin A hypohidrotic ectodermal dysplasia novel mutation prenatal diagnosis whole exome sequencing Genetics QH426-470 Kang Yu Yihan Shen Cai‐Ling Jiang Wei Huang Feng Wang Yi‐Qun Wu Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
description	Abstract Background Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (EDA) gene mutation. Fetus with genetic deficiency of EDA can be prenatally corrected. This study aimed at revealing the pathogenesis of two HED families and making a prenatal diagnosis for one pregnant female carrier. Designs Genomic DNA was extracted from two HED patients and sequenced using whole exome sequencing (WES). The detected mutations were confirmed in patients and family members using Sanger sequencing. The expression of soluble ectodysplasin A1 (EDA1) protein was studied by western blot. The transcriptional activity of NF‐κB pathway was tested by dual luciferase assay. The genomic DNA of fetus was extracted from shed chorion cells and EDA gene was screened through Sanger sequencing. Results We identified two novel EDA mutations: c.1136T>C (p.Phe379Ser) and c.[866G>C;868A>T] (p.[Arg289Pro;Ser290Cys]). Further examinations revealed that these two mutated EDA1 proteins showed completely impaired solubility, and the transcriptional NF‐κB activation induced by these missense mutant‐type EDA1 proteins was significantly reduced compared with wild‐type EDA1. Furthermore, the analysis of amniotic fluid samples from a pregnant heterozygote indicated that the fetus was a c.1136T>C mutation female carrier. Conclusions This study extended the mutation spectrum of X‐linked hypohidrotic ectodermal dysplasia (XLHED) and applied prenatal diagnosis for the pregnant carrier, which can be helpful in genetic counseling, prenatal diagnosis, and intervention for the XLHED family.
format	article
author	Kang Yu Yihan Shen Cai‐Ling Jiang Wei Huang Feng Wang Yi‐Qun Wu
author_facet	Kang Yu Yihan Shen Cai‐Ling Jiang Wei Huang Feng Wang Yi‐Qun Wu
author_sort	Kang Yu
title	Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
title_short	Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
title_full	Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
title_fullStr	Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
title_full_unstemmed	Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia
title_sort	two novel ectodysplasin a gene mutations and prenatal diagnosis of x‐linked hypohidrotic ectodermal dysplasia
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/123e024150934c0598559367208389b9
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Two novel ectodysplasin A gene mutations and prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia

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