{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:51:10Z","timestamp":1762005070145,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T00:00:00Z","timestamp":1526860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden death. Currently 60% of patients meeting Task Force Criteria (TFC) have an identifiable mutation in one of the desmosomal genes. As much overlap is described between other cardiomyopathies and ARVC, we examined the prevalence of rare, possibly pathogenic sarcomere variants in the ARVC population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred and thirty\u2010seven (137) individuals meeting 2010 TFC for a diagnosis of ARVC, negative for pathogenic desmosomal variants, <jats:italic>TMEM43<\/jats:italic>, <jats:italic>SCN5A<\/jats:italic>, and <jats:italic>PLN<\/jats:italic> were screened for variants in the sarcomere genes (<jats:italic>ACTC1<\/jats:italic>, <jats:italic>MYBPC3<\/jats:italic>, <jats:italic>MYH7<\/jats:italic>, <jats:italic>MYL2<\/jats:italic>, <jats:italic>MYL3<\/jats:italic>, <jats:italic>TNNC1<\/jats:italic>, <jats:italic>TNNI3<\/jats:italic>, <jats:italic>TNNT2<\/jats:italic>, and <jats:italic>TPM1<\/jats:italic>) through either clinical or research genetic testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six probands (6\/137, 4%) were found to carry rare variants in the sarcomere genes. These variants have low prevalence in controls, are predicted damaging by Polyphen\u20102, and some of the variants are known pathogenic hypertrophic cardiomyopathy mutations. Sarcomere variant carriers had a phenotype that did not differ significantly from desmosomal mutation carriers. As most of these probands were the only affected individuals in their families, however, segregation data are noninformative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data show variants in the sarcomere can be identified in individuals with an ARVC phenotype. Although rare and predicted damaging, proven functional and segregational evidence that these variants can cause ARVC is lacking. Therefore, caution is warranted in interpreting these variants when identified on large next\u2010generation sequencing panels for cardiomyopathies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.13621","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T19:50:47Z","timestamp":1525117847000},"page":"1004-1009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of sarcomeric variants in probands with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC)"],"prefix":"10.1111","volume":"29","author":[{"given":"Brittney","family":"Murray","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar T.","family":"Hoorntje","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Netherlands Heart Institute  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneline S. J. M.","family":"te Riele","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute  Utrecht the Netherlands"},{"name":"Division of Cardiology University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen F.","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Division of Cardiology University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harikrishna","family":"Tandri","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan D. H.","family":"Jongbloed","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A. M.","family":"Wilde","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre, Heart Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard N. W.","family":"Hauer","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute  Utrecht the Netherlands"},{"name":"Division of Cardiology University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-9433","authenticated-orcid":false,"given":"Hugh","family":"Calkins","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia A.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-6749","authenticated-orcid":false,"given":"J. Peter","family":"van Tintelen","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute  Utrecht the Netherlands"},{"name":"Department of Clinical Genetics, Amsterdam Cardiovascular Sciences Academic Medical Center, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Dooijes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.542266"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu509"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.001003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001605"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs373"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs119"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw234"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309396"},{"key":"e_1_2_7_10_1","first-page":"1063","article-title":"Arrhythmogenic right ventricular cardiomyopathy: Implications of next\u2010generation sequencing in appropriate diagnosis","volume":"9","author":"Medeiros\u2010Domingo A","year":"2016","journal-title":"Europace"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq025"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0403-7"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu284"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:6<385::AID-HUMU4>3.0.CO;2-E"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2012.09.002"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.03.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2011.0214"}],"container-title":["Journal of Cardiovascular Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjce.13621","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jce.13621","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T01:20:05Z","timestamp":1695000005000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jce.13621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,21]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1111\/jce.13621"],"URL":"https:\/\/doi.org\/10.1111\/jce.13621","archive":["Portico"],"relation":{},"ISSN":["1045-3873","1540-8167"],"issn-type":[{"type":"print","value":"1045-3873"},{"type":"electronic","value":"1540-8167"}],"subject":[],"published":{"date-parts":[[2018,5,21]]},"assertion":[{"value":"2018-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}