{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T15:37:53Z","timestamp":1768750673895,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500828"],"award-info":[{"award-number":["81500828"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypohidrotic ectodermal dysplasia (HED) mainly results from gene mutations in the EDA\/EDAR\/NF\u2010\u03baB pathway. Function analysis of the mutations in the collagen domain of ectodysplasin A (EDA)result in HED has been rarely studied. This study aimed at determining the mechanism by which the novel collagen domain mutation of EDA results in HED.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the DNAs from a Chinese family with HED and performed bioinformatics analysis. A new three\u2010dimensional structure model of the EDA trimer was built and used to predict the effect of the mutations on EDA. We performed a western blot to detect EDA1 proteins in cell lysates and supernatants. We then performed coimmunoprecipitation to determine whether the mutation would affect the interaction of EDA1 with the EDA receptor (EDAR). Dual luciferase reporter assay and immunofluorescence were performed to detect the effect of the mutant EDA1 protein on nuclear factor kappa B (NF\u2010\u03baB) activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense mutation (c.593G\u2009&gt;\u2009A, p. Gly198Glu) in the collagen domain of EDA was detected. The mutation was predicted to be disease\u2010causing. A three\u2010dimensional structure model of the EDA trimer was first built in this study, in which the mutation site is located around the receptor binding domain. Functional studies showed that there was no difference in the secretion activity between the mutant EDA1 and the wild\u2010type EDA1. However, the receptor\u2010binding activity and the transcription activation of NF\u2010\u03baB were impaired by the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified a novel mutation (c.593G\u2009&gt;\u2009A, p. Gly198Glu) in the collagen domain of EDA. Bioinformatics analysis and functional studies showed this mutation was damaging, indicating that mutations in the collagen domain of EDA could result in HED by affecting the receptor\u2010binding activity of EDA and the transcriptional activity of NF\u2010\u03baB.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2119","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:48:51Z","timestamp":1669794531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel mutation in the collagen domain of <scp>EDA<\/scp> results in hypohidrotic ectodermal dysplasia by impacting the receptor\u2010binding capability"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6050-0643","authenticated-orcid":false,"given":"Xingyu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Laboratory for Digital and Material Technology of Stomatology &amp; Central Laboratory Peking University School and Hospital of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Laboratory for Digital and Material Technology of Stomatology &amp; Central Laboratory Peking University School and Hospital of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Laboratory for Digital and Material Technology of Stomatology &amp; Central Laboratory Peking University School and Hospital of Stomatology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109969(92)90110\u2010t"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21384"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.21.3403"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100722.2008.00555.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/414913a"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2011.00061"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0162\u20103109(99)00011\u20109"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010019\u20101251\u2010x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.127"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746\u2010160x\u20108\u2010s1\u2010p5"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11030239"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.14048"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02278"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101280200"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154884"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.20.2371"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32864"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019244"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37412"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12376"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2119","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2119","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:10:58Z","timestamp":1692655858000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/mgg3.2119"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2119","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]},"assertion":[{"value":"2022-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2119"}}