{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:27Z","timestamp":1788447747527,"version":"build-2803163510"},"reference-count":25,"publisher":"BMJ","issue":"2","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901919"],"award-info":[{"award-number":["81901919"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81920108021"],"award-info":[{"award-number":["81920108021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970200"],"award-info":[{"award-number":["81970200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271609"],"award-info":[{"award-number":["82271609"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"crossref","award":["2023B01J1011"],"award-info":[{"award-number":["2023B01J1011"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,6,18]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 150 unrelated deceased Chinese were collected for whole-exome sequencing, with analysis focusing on a panel of 118 genes associated with \u2018abnormal mitral valve morphology\u2019. Cases were prespecified as \u2018longitudinally extensive MAD (LE-MAD)\u2019 or \u2018longitudinally less-extensive MAD (LLE-MAD)\u2019 according to the gross disjunctional length with a cut-off of 4.0 mm. The pedigree investigation was conducted on a case carrying an ultra-rare (minor allele frequency &lt;0.1%) deleterious variant in <jats:italic>DCHS1<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-seven ultra-rare deleterious variants were finally identified. Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were <jats:italic>ANK1<\/jats:italic>, <jats:italic>COL3A1<\/jats:italic>, <jats:italic>DCHS1<\/jats:italic>, <jats:italic>FBN2<\/jats:italic>, <jats:italic>GNPTAB<\/jats:italic>, <jats:italic>LZTR1<\/jats:italic>, <jats:italic>PLD1<\/jats:italic>, <jats:italic>RYR1<\/jats:italic> and <jats:italic>VPS13B<\/jats:italic>. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p&lt;0.001), and the only gene related to LE-MAD with borderline significance was <jats:italic>DCHS1<\/jats:italic>. LE-MAD was consistently observed in a sizeable Chinese family, in which LE-MAD independently co-segregated with an ultra-rare deleterious variant in <jats:italic>DCHS1<\/jats:italic>, rs145429962.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study initially proposed that isolated LE-MAD might be a particular phenotype of MAD with a complex genetic predisposition. Deleterious variants in <jats:italic>DCHS1<\/jats:italic> might be associated with the morphogenesis of LE-MAD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109278","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T14:08:04Z","timestamp":1688393284000},"page":"125-131","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Mutation in mitral valve prolapse susceptible gene <i>DCHS1<\/i> causes familial mitral annular disjunction"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-8643","authenticated-orcid":false,"given":"Nan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, China"},{"name":"Department of Cardiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China"},{"name":"Guangzhou Key Laboratory of Molecular Mechanisms and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianding","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China"},{"name":"Guangzhou Key Laboratory of Molecular Mechanisms and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"2025101712473871000_61.2.125.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198602273140902"},{"key":"2025101712473871000_61.2.125.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2016.11.022"},{"key":"2025101712473871000_61.2.125.3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034075"},{"key":"2025101712473871000_61.2.125.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.07.070"},{"key":"2025101712473871000_61.2.125.5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jacc.2020.10.051","article-title":"Association of mitral annular disjunction with premature cardiac mortality in a large series of autopsies","volume":"77","author":"Zhou","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2025101712473871000_61.2.125.6","first-page":"174","article-title":"Does anatomic phenotype of mitral annular disjunction impact survival? 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