{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T21:43:59Z","timestamp":1778190239686,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FoRUM, Ruhr-University Bochum","award":["F842R-2015"],"award-info":[{"award-number":["F842R-2015"]}]},{"name":"Erich &amp; Hanna Klessmann Foundation, G\u00fctersloh, Germany","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them TTN and RBM20. Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in TTN (TTNtv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 (RBM20) are also known to be associated with severe cardiomyopathies. TTN is one of the major RBM20 splicing targets. Most of the pathogenic RBM20 mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant RBM20. Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic TTN and RBM20 mutations. We show that the splicing of RBM20 target genes is affected in the mutation carrier. Furthermore, we reveal RBM20 haploinsufficiency presumably caused by the frameshift mutation in RBM20.<\/jats:p>","DOI":"10.3390\/genes12060883","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T12:08:55Z","timestamp":1623154135000},"page":"883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6899-7693","authenticated-orcid":false,"given":"Anna","family":"Gaertner","sequence":"first","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bloebaum","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-2343","authenticated-orcid":false,"given":"Andreas","family":"Brodehl","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baerbel","family":"Klauke","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Sielemann","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Kassner","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-8715","authenticated-orcid":false,"given":"Henrik","family":"Fox","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel","family":"Morshuis","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Tiesmeier","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Schulz","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-112X","authenticated-orcid":false,"given":"Ralph","family":"Knoell","sequence":"additional","affiliation":[{"name":"Bioscience, Cardiovascular, Renal & Metabolism, BioPharmaceuticals R&D, AstraZeneca, SE-431 50 Gothenburg, Sweden"},{"name":"Department of Medicine (MedH), Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institute, SE-171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Gummert","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Milting","sequence":"additional","affiliation":[{"name":"Herz-und Diabeteszentrum NRW, Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum, Klinik f\u00fcr Thorax- und Kardiovaskularchirurgie, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Erich und Hanna Klessmann-Institut f\u00fcr Kardiovaskul\u00e4re Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrcardio.2013.105","article-title":"Dilated cardiomyopathy: The complexity of a diverse genetic architecture","volume":"10","author":"Hershberger","year":"2013","journal-title":"Nat. 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