{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:54Z","timestamp":1753869714744,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (<jats:italic>EDA<\/jats:italic>) gene mutation. Fetus with genetic deficiency of <jats:italic>EDA<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Designs<\/jats:title><jats:p>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\u2010\u03baB pathway was tested by dual luciferase assay. The genomic DNA of fetus was extracted from shed chorion cells and <jats:italic>EDA<\/jats:italic> gene was screened through Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two novel <jats:italic>EDA<\/jats:italic> mutations: c.1136T&gt;C (p.Phe379Ser) and c.[866G&gt;C;868A&gt;T] (p.[Arg289Pro;Ser290Cys]). Further examinations revealed that these two mutated EDA1 proteins showed completely impaired solubility, and the transcriptional NF\u2010\u03baB activation induced by these missense mutant\u2010type EDA1 proteins was significantly reduced compared with wild\u2010type EDA1. Furthermore, the analysis of amniotic fluid samples from a pregnant heterozygote indicated that the fetus was a c.1136T&gt;C mutation female carrier.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study extended the mutation spectrum of X\u2010linked 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1824","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T12:48:48Z","timestamp":1632833328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Two novel ectodysplasin A gene mutations and prenatal diagnosis of X\u2010linked hypohidrotic ectodermal dysplasia"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-6515","authenticated-orcid":false,"given":"Kang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Second Dental Center Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Second Dental Center Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai\u2010Ling","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Second Dental Center Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oral Implantology Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Implantology Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-6256","authenticated-orcid":false,"given":"Yi\u2010Qun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Second Dental Center Ninth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology National Clinical Research Center of Stomatology Shanghai 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