{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:41:06Z","timestamp":1768747266784,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"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;amp; Gen Med"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is mainly associated with mutations in the <jats:italic>EDA<\/jats:italic>, <jats:italic>EDAR<\/jats:italic>, and <jats:italic>EDARADD<\/jats:italic> responsible for the development of ectodermal\u2010derived structures. HED displays different modes of inheritance according to the gene that is involved, with X\u2010linked EDA\u2010related HED being the most frequent form of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two families with tooth agenesis and manifestations of HED underwent clinical examination and <jats:italic>EDA<\/jats:italic>, <jats:italic>EDAR<\/jats:italic>, and <jats:italic>EDARADD<\/jats:italic> genetic analysis. The impact of the novel variant on the protein was evaluated through bioinformatics tools, whereas molecular modeling was used to predict the effect on the protein structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense variant was identified in the <jats:italic>EDAR<\/jats:italic> (c.287T&gt;C, p.Phe96Ser) of a female child proband and her mother, accounting for autosomal dominant HED. The genetic variant c.866G&gt;A (p.Arg289His) in <jats:italic>EDA<\/jats:italic>, which has been previously described, was observed in the male proband of another family confirming its role in X\u2010linked HED. The inheritance model of the missense mutation showed a different relationship with X\u2010linked HED and non\u2010syndromic tooth agenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1555","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T18:58:22Z","timestamp":1605725902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Missense mutations in <i>EDA<\/i> and <i>EDAR<\/i> genes cause dominant syndromic tooth 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