{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:38:26Z","timestamp":1783726706959,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013699","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft und Forschung","doi-asserted-by":"publisher","award":["01EO1504."],"award-info":[{"award-number":["01EO1504."]}],"id":[{"id":"10.13039\/501100013699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG; Ma 2528\/7-1, SFB-894, TRR-219"],"award-info":[{"award-number":["DFG; Ma 2528\/7-1, SFB-894, TRR-219"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Inherited cardiomyopathies are characterized by clinical and genetic heterogeneity that challenge genetic diagnostics. In this study, we examined the diagnostic benefit of exome data compared to targeted gene panel analyses, and we propose new candidate genes. We performed exome sequencing in a cohort of 61 consecutive patients with a diagnosis of cardiomyopathy or primary arrhythmia, and we analyzed the data following a stepwise approach. Overall, in 64% of patients, a variant of interest (VOI) was detected. The detection rate in the main sub-cohort consisting of patients with dilated cardiomyopathy (DCM) was much higher than previously reported (25\/36; 69%). The majority of VOIs were found in disease-specific panels, while a further analysis of an extended panel and exome data led to an additional diagnostic yield of 13% and 5%, respectively. Exome data analysis also detected variants in candidate genes whose functional profile suggested a probable pathogenetic role, the strongest candidate being a truncating variant in STK38. In conclusion, although the diagnostic yield of gene panels is acceptable for routine diagnostics, the genetic heterogeneity of cardiomyopathies and the presence of still-unknown causes favor exome sequencing, which enables the detection of interesting phenotype\u2013genotype correlations, as well as the identification of novel candidate genes.<\/jats:p>","DOI":"10.3390\/jcm9072168","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"2168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["New Insights on Genetic Diagnostics in Cardiomyopathy and Arrhythmia Patients Gained by Stepwise Exome Data Analysis"],"prefix":"10.3390","volume":"9","author":[{"given":"Konstantinos","family":"Kolokotronis","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Pluta","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Klopocki","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdmute","family":"Kunstmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-5004","authenticated-orcid":false,"given":"Daniel","family":"Messroghli","sequence":"additional","affiliation":[{"name":"German Heart Center Berlin, Department of Internal Medicine-Cardiology, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Maack","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Comprehensive Heart Failure Center (CHFC), University Clinic W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Tejman-Yarden","sequence":"additional","affiliation":[{"name":"The Safra International Congenital Heart Center. Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Ramat Gan 5365601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Arad","sequence":"additional","affiliation":[{"name":"Heart Failure Institute and Leviev Heart Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Ramat Gan 5365601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Rost","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1363-8826","authenticated-orcid":false,"given":"Brenda","family":"Gerull","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Genetics, Comprehensive Heart Failure Center (CHFC) and Department of Medicine I, University Clinic W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1161\/CIRCULATIONAHA.106.174287","article-title":"Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention","volume":"113","author":"Maron","year":"2006","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra0902923","article-title":"Inherited cardiomyopathies","volume":"364","author":"Watkins","year":"2011","journal-title":"N. 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