{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:34:19Z","timestamp":1772987659162,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T00:00:00Z","timestamp":1625356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by hypohidrosis, hypodontia, and hypotrichosis. Autosomal forms of the disease are caused by mutations in either <jats:italic>EDAR<\/jats:italic> or <jats:italic>EDARADD<\/jats:italic>. To date, the underlying pathomechanisms for HED resulting from <jats:italic>EDARADD<\/jats:italic> mutations have not fully been disclosed. In this study, we performed detailed <jats:italic>in vitro<\/jats:italic> analyses in order to characterize three dominantly inherited missense mutations, p.D120Y, p.L122R, and p.D123N, and one recessively inherited missense mutation, p.E152K, in the <jats:italic>EDARADD<\/jats:italic> gene. Nuclear factor (NF)\u2010\u03baB reporter assays demonstrated that all the mutant EDARADD showed reduction in activation of NF\u2010\u03baB. Importantly, p.D120Y\u2010, p.L122R\u2010, and p.D123N\u2010mutant EDARADD slightly reduced the NF\u2010\u03baB activity induced by wild\u2010type EDARADD in a dominant negative manner. Co\u2010immunoprecipitation assays showed that all of the mutant EDARADD were capable of binding to EDAR and wild\u2010type EDARADD. Additional co\u2010immunoprecipitation assays revealed that p.D120Y\u2010, p.L122R\u2010, and p.D123N\u2010mutant EDARADD markedly prevented the interaction between EDAR and wild\u2010type EDARADD, which further indicated a dominant negative effect by these mutations. Finally, we found that p.D120Y\u2010, p.L122R\u2010, and p.D123N\u2010mutant EDARADD completely lost the ability to bind with TRAF6, while p.E152K\u2010mutant EDARADD showed a mild reduction in the affinity. Our findings will provide crucial information toward unraveling the molecular mechanisms how <jats:italic>EDARADD<\/jats:italic> gene mutations cause the disease.<\/jats:p>","DOI":"10.1111\/1346-8138.16044","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:11:11Z","timestamp":1625465471000},"page":"1533-1541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterization of <i>EDARADD<\/i> gene mutations responsible for hypohidrotic ectodermal dysplasia"],"prefix":"10.1111","volume":"48","author":[{"given":"Nobuyuki","family":"Asano","sequence":"first","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichiro","family":"Yasuno","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine 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