• James S Ware, Jian Li, Erica Mazaika, Christopher M Yasso, Tiffany DeSouza, Thomas P Cappola, Emily J Tsai, Denise Hilfiker-Kleiner, Chizuko A Kamiya, Francesco Mazzarotto, Stuart A Cook, Indrani Halder, Sanjay K Prasad, Jessica Pisarcik, Karen Hanley-Yanez, Rami Alharethi, Julie Damp, Eileen Hsich, Uri Elkayam, Richard Sheppard, Angela Kealey, Jeffrey Alexis, Gautam Ramani, Jordan Safirstein, John Boehmer, Daniel F Pauly, Ilan S Wittstein, Vinay Thohan, Mark J Zucker, Peter Liu, John Gorcsan, Dennis M McNamara, Christine E Seidman, Jonathan G Seidman, Zoltan Arany, and IMAC-2 and IPAC Investigators.
• From the Department of Genetics, Harvard Medical School (J.S.W., E.M., C.M.Y., C.E.S., J.G.S.), the Howard Hughes Medical Institute (C.E.S.), and the Cardiovascular Division, Brigham and Women's Hospital (J.S.W., E.M., C.E.S., J.G.S.) - all in Boston; the Cardiovascular Institute and the Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.L., T.D., T.P.C., Z.A.), the Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh (I.H., J.P., K.H.-Y., J.G., D.M.M.), and Penn State Hershey Medical Center, Hershey (J.B.) - all in Pennsylvania; the National Institute for Health Research Royal Brompton Cardiovascular Biomedical Research Unit (J.S.W., F.M., S.K.P.) and the National Heart and Lung Institute (J.S.W., F.M., S.A.C., S.K.P.), Imperial College London, London; the Division of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York (E.J.T.), and the University of Rochester, Rochester (J.A.) - both in New York; the Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (D.H.-K.); the Department of Perinatology and Gynecology, the National Cerebral and Cardiovascular Center, Osaka, Japan (C.A.K.); the National Heart Center and Duke-National University of Singapore, Singapore (S.A.C.); the Intermountain Medical Center, Murray, Utah (R.A.); Vanderbilt University, Nashville (J.D.); Cleveland Clinic, Cleveland (E.H.); University of Southern California, Los Angeles (U.E.); McGill University and Jewish General Hospital, Montreal (R.S.), University of Calgary, Calgary, AB (A.K.), and University of Toronto, Toronto (P.L.) - all in Canada; University of Maryland, College Park (G.R.), and Johns Hopkins Hospital, Baltimore (I.S.W.) - both in Maryland; Morristown Hospital, Morristown (J.S.), and Newark Beth Israel Medical Center, Newark (M.J.Z.) - both in New Jersey; Truman Medical Center, University of Missouri, Kansas City (D.F.P.); and Wa
• N. Engl. J. Med. 2016 Jan 21; 374 (3): 233-41.

AbstractBackground Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

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