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We studied whether tTTN variants are associated with a clinically distinguishable form of DCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We compared clinical data on DCM probands and relatives with a tTTN mutation (n = 45, n = 73), LMNA mutation (n = 28, n = 29), and probands who tested negative for both genes [idiopathic DCM (iDCM); n = 60]. Median follow-up was at least 2.5\u2009years in each group. TTN subjects presented with DCM at higher age than LMNA subjects (probands 47.9 vs. 40.4\u2009years, P = 0.004; relatives 59.8 vs. 47.0\u2009years, P = 0.01), less often developed LVEF &amp;lt;35% [probands hazard ratio (HR) 0.38, P = 0.002], had higher age of death (probands 70.4 vs. 59.4\u2009years, P &amp;lt; 0.001; relatives 74.1 vs. 58.4\u2009years, P = 0.008), and had better composite outcome (malignant ventricular arrhythmia, heart transplantation, or death; probands HR 0.09, P &amp;lt; 0.001; relatives HR 0.21, P = 0.02) than LMNA subjects and iDCM subjects (HR 0.36, P = 0.07). An LVEF increase of at least 10% occurred in 46.9% of TTN subjects after initiation of standard heart failure treatment, while this only occurred in 6.5% of LMNA subjects (P &amp;lt; 0.001) and 18.5% of iDCM subjects (P = 0.02). This was confirmed in families with co-segregation, in which the 10% point LVEF increase occurred in 55.6% of subjects (P = 0.003 vs. LMNA, P = 0.079 vs. iDCM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows that tTTN-associated DCM is less severe at presentation and more amenable to standard therapy than LMNA mutation-induced DCM or iDCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.673","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:25:24Z","timestamp":1478219124000},"page":"512-521","source":"Crossref","is-referenced-by-count":165,"title":["Truncating Titin Mutations are Associated with a Mild and Treatable form of Dilated Cardiomyopathy"],"prefix":"10.1093","volume":"19","author":[{"given":"Joeri A.","family":"Jansweijer","sequence":"first","affiliation":[{"name":"AMC Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Nieuwhof","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar T.","family":"Hoorntje","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan D.H.","family":"Jongbloed","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald H.","family":"Lekanne Deprez","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex V.","family":"Postma","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Embryology and Physiology, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Bronk","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid A.W.","family":"van Rijsingen","sequence":"additional","affiliation":[{"name":"AMC Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"de Haij","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Biagini","sequence":"additional","affiliation":[{"name":"Department of Cardiology, S. Orsola-Malpighi Hospital , Bologna University ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"van Haelst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Antonius Hospital , Sneek ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Wijngaarden","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Deventer Hospital , Deventer ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.M.","family":"Wilde","sequence":"additional","affiliation":[{"name":"AMC Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel M.A.M.","family":"Mannens","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Y.","family":"van Spaendonck-Zwarts","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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