{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:32:48Z","timestamp":1793410368586,"version":"4.5.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              Variants in the cardiomyocyte-specific RNA splicing factor\n              <jats:italic>RBM20<\/jats:italic>\n              have been linked to familial cardiomyopathy, but the causative genetic architecture and clinical consequences of this disease are incompletely defined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>\n              To define the genetic architecture of\n              <jats:italic>RBM20<\/jats:italic>\n              cardiomyopathy, we first established a database of\n              <jats:italic>RBM20<\/jats:italic>\n              variants associated with cardiomyopathy and compared these to variants observed in the general population with respect to their location in the\n              <jats:italic>RBM20<\/jats:italic>\n              coding transcript. We identified 2 regions significantly enriched for cardiomyopathy-associated variants in exons 9 and 11. We then assembled a registry of 74 patients with\n              <jats:italic>RBM20<\/jats:italic>\n              variants from 8 institutions across the world (44 index cases and 30 from cascade testing). This\n              <jats:italic>RBM20<\/jats:italic>\n              patient registry revealed highly prevalent family history of sudden cardiac death (51%) and cardiomyopathy (72%) among index cases and a high prevalence of composite arrhythmias (including atrial fibrillation, nonsustained ventricular tachycardia, implantable cardiac defibrillator discharge, and sudden cardiac arrest, 43%). Patients harboring variants in cardiomyopathy-enriched regions identified by our variant database analysis were enriched for these findings. Further, these characteristics were more prevalent in the\n              <jats:italic>RBM20<\/jats:italic>\n              registry than in large cohorts of patients with dilated cardiomyopathy and\n              <jats:italic>TTNtv<\/jats:italic>\n              cardiomyopathy and not significantly different from a cohort of patients with\n              <jats:italic>LMNA<\/jats:italic>\n              -associated cardiomyopathy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              Our data establish\n              <jats:italic>RBM20<\/jats:italic>\n              cardiomyopathy as a highly penetrant and arrhythmogenic cardiomyopathy. These findings underline the importance of arrhythmia surveillance and family screening in this disease and represent the first step in defining the genetic architecture of\n              <jats:italic>RBM20<\/jats:italic>\n              disease causality on a population level.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.118.005371","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T09:00:36Z","timestamp":1552640436000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["Regional Variation in\n            <i>RBM20<\/i>\n            Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy"],"prefix":"10.1161","volume":"12","author":[{"given":"Victoria N.","family":"Parikh","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine (V.N.P., C.C., C.R., M.T.W., E.A.A.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Caleshu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine (V.N.P., C.C., C.R., M.T.W., E.A.A.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Reuter","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine (V.N.P., C.C., C.R., M.T.W., E.A.A.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences (L.C.L.), Stanford University School of Medicine, CA."},{"name":"Department of Biomedical Data Science (L.C.L.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Ingles","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Royal Prince Alfred Hospital and Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, University of Sydney, New South Wales, Australia (J.I., C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Garcia","sequence":"additional","affiliation":[{"name":"Invitae, Inc, San Francisco, CA (J.G., R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"McCaleb","sequence":"additional","affiliation":[{"name":"Genomic Health, Inc, Redwood City, CA (K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolulope","family":"Adesiyun","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, MD (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farbod","family":"Sedaghat-Hamedani","sequence":"additional","affiliation":[{"name":"Institute for Cardiomyopathies, University Hospital Heidelberg, German Center for Cardiovascular Research (F.S.-H., B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Partners Health Care and Harvard Medical School, Boston, MA (S.K., N.K.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Graw","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora (S.G., M.R.G.T., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gigli","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Integrata, University of 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