{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:41:46Z","timestamp":1791315706862,"version":"4.3.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Truncating variants in desmoplakin (\n                      <jats:italic>DSP<\/jats:italic>\n                      tv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of\n                      <jats:italic>DSP<\/jats:italic>\n                      tv cardiomyopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Individuals with\n                      <jats:italic>DSP<\/jats:italic>\n                      tv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported\n                      <jats:italic>DSP<\/jats:italic>\n                      tv performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      There were 98 probands and 72 family members (mean age at diagnosis 43\u00b18 years, 59% women) with a\n                      <jats:italic>DSP<\/jats:italic>\n                      tv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals.\n                      <jats:italic>DSP<\/jats:italic>\n                      tv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major\n                      <jats:italic>DSP<\/jats:italic>\n                      isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      In the largest series of individuals with\n                      <jats:italic>DSP<\/jats:italic>\n                      tv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.121.003672","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T11:26:46Z","timestamp":1672313206000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (\n                    <i>DSP<\/i>\n                    ) Truncating Variant"],"prefix":"10.1161","volume":"16","author":[{"given":"Edgar T.","family":"Hoorntje","sequence":"first","affiliation":[{"name":"Department of Genetics, University Medical Centre Groningen, University of Groningen (E.T.H., G.J.t.M., J.D.H.J.)."},{"name":"Netherlands Heart Institute, Utrecht, the Netherlands (E.T.H., L.P.B., L.L., J.P.v.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Burns","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute (C.B., B.G., R.D.B., C.S.)."},{"name":"Faculty of Medicine and Health (C.B., B.G., R.D.B., J.D., C.S., L.Y., J.I.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (C.B., B.G., C.S., L.Y., J.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-541X","authenticated-orcid":true,"given":"Luisa","family":"Marsili","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam University Medical Centre, location AMC, University of Amsterdam, the Netherlands (L.M., J.P.v.T.)."},{"name":"Clinique de G\u00e9n\u00e9tique, CHU Lille, Lille, France (L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Corden","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and MRC London Institute of Medical Science, Imperial College London and Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK (B.C., A.L., N.W., J.S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-5559","authenticated-orcid":true,"given":"Victoria N.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Stanford Centre for Inherited Cardiovascular Disease, Department of Medicine, Stanford University School of Medicine, CA (V.N.P., C.R., E.A.A., M.T.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-8304","authenticated-orcid":true,"given":"Gerard J.","family":"te Meerman","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Centre Groningen, University of Groningen (E.T.H., G.J.t.M., J.D.H.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-0329","authenticated-orcid":true,"given":"Belinda","family":"Gray","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute (C.B., B.G., R.D.B., C.S.)."},{"name":"Faculty of Medicine and Health (C.B., B.G., R.D.B., J.D., C.S., L.Y., J.I.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (C.B., B.G., C.S., L.Y., J.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Adiyaman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Isala Heart Center, Zwolle (A.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-9864","authenticated-orcid":true,"given":"Richard D.","family":"Bagnall","sequence":"additional","affiliation":[{"name":"Agnes Ginges Centre for Molecular Cardiology at Centenary Institute (C.B., B.G., R.D.B., C.S.)."},{"name":"Faculty of Medicine and Health (C.B., B.G., R.D.B., J.D., C.S., L.Y., J.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-4293","authenticated-orcid":true,"given":"Daniela Q.C.M.","family":"Barge-Schaapveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre (D.Q.C.M.B.-S., A.M.v.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-2998","authenticated-orcid":true,"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen (M.P.v.d.B., 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J.P.v.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freyja H.M.","family":"van Lint","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Utrecht, University Medical Centre Utrecht, the Netherlands (F.H.M.v.L., J.P.v.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5653-8211","authenticated-orcid":true,"given":"Amrit","family":"Lota","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and MRC London Institute of Medical Science, Imperial College London and Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, UK (B.C., A.L., N.W., J.S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-4641","authenticated-orcid":true,"given":"Carlo","family":"Marcelis","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboud University Medical 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