{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:04:54Z","timestamp":1792004694174,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,10]],"date-time":"2017-12-10T00:00:00Z","timestamp":1512864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","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":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A recent study identified <jats:italic><jats:styled-content style=\"fixed-case\">DCHS<\/jats:styled-content>1<\/jats:italic> as a causal gene for mitral valve prolapse. The goal of this study is to investigate the presence and frequency of known and novel variants in this gene in 100 asymptomatic patients with moderate to severe organic mitral regurgitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing assays were developed for two previously identified functional missense variants, namely p.R2330C and p.R2513H, and all 21 exons of <jats:italic><jats:styled-content style=\"fixed-case\">DCHS<\/jats:styled-content>1<\/jats:italic>. Pathogenicity of variants was evaluated in silico.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>p.R2330C and p.R2513H were not identified in this cohort. Sequencing all coding regions revealed eight missense variants including six considered deleterious. This includes one novel variant (p.A2464P) and two rare variants (p.R2770Q and p.R2462Q). These variants are predicted to be deleterious with combined annotation\u2010dependent depletion (<jats:styled-content style=\"fixed-case\">CADD<\/jats:styled-content>) scores greater than 25, which are in the same range as p.R2330C (<jats:styled-content style=\"fixed-case\">CADD<\/jats:styled-content>\u00a0=\u00a028.0) and p.R2513H (<jats:styled-content style=\"fixed-case\">CADD<\/jats:styled-content>\u00a0=\u00a024.3). More globally, 24 of 100 cases were carriers of at least one in silico\u2010predicted deleterious missense variant in <jats:italic><jats:styled-content style=\"fixed-case\">DCHS<\/jats:styled-content>1<\/jats:italic>, suggesting that this single gene may account for a substantial portion of cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reveals an important contribution of germline variants in <jats:italic><jats:styled-content style=\"fixed-case\">DCHS<\/jats:styled-content>1<\/jats:italic> in unrelated patients with mitral valve prolapse and supports genetic testing of this gene to screen individuals at risk.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.347","type":"journal-article","created":{"date-parts":[[2017,12,10]],"date-time":"2017-12-10T05:11:37Z","timestamp":1512882697000},"page":"114-120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Deleterious variants in <i><scp>DCHS<\/scp>1<\/i> are prevalent in sporadic cases of mitral valve prolapse"],"prefix":"10.1002","volume":"6","author":[{"given":"Alisson","family":"Clemenceau","sequence":"first","affiliation":[{"name":"Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec Quebec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"B\u00e9rub\u00e9","sequence":"additional","affiliation":[{"name":"Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec Quebec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam\u00e9la","family":"B\u00e9langer","sequence":"additional","affiliation":[{"name":"Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec Quebec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Institut Universitaire de Cardiologie et de Pneumologie de 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