Peer-Reviewed Publication
Sci Transl Med2026;18(867):eaea2747.September 16, 2026Journal Article
The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes.
Eleonora Adami1,2, Yuri Kim3,4, Sean L Zheng5,6,7, Nikolay Shvetsov1, Corinna Losert8,9, Henrike Maatz1,2, Syndi Barish10, Gabriela Venturini10, Natalia López Anguita1, Qi Shi5,6, Meraj Neyazi10,11,12, Martin Beyer10,12,13, Eric Q Wei3,10, Amanda Adam14,15, Abhilash Suresh10, Daniel Reichart10,16,17,18, Eric Lindberg1,18,19, Kemar J Brown10,20, Viktoria Strohmenger10,21, David Saul3,4, Anna Gärtner22, Michael Lee5, Lukas Mach5,23, Jan Lukas Robertus24, Joshua M Gorham10, Jan Haas25,26,27, Laura A Liebig1, Christoph Lippert28,29, Benjamin Meder25,26,27, Anna Myronova1, Giannino Patone1, Sam N Barnett5,23, James S Ware5,6, Fabio de Robertis24, Antonis Pantazis24, Jan Gummert22, Anissa Viveiros14,15, Huachen Chen14,15, Jorge Ruiz-Orera1, Norbert Frey27,30,31, Barbara A McDonough3,10, Richard N Mitchell32, Robert F Padera32, Sharlene M Day33, Carolyn Y Ho3, Neal K Lakdawala3, Hendrik Milting22, Matthias Heinig8,9,17, Gavin Y Oudit14,15, Michela Noseda5,23, Jonathan G Seidman10, Norbert Hübner1,2,31,34, Christine E Seidman3,10
1Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany.
2German Center for Cardiovascular Research (DZHK), Partner Site Berlin. Berlin 13125, Germany.
3Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
4Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
5National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
6Medical Research Council Laboratory of Medical Sciences, London W12 0NN, UK.
7British Heart Foundation Centre of Regenerative Medicine, British Heart Foundation Centre of Research Excellence, Imperial College London, London W12 0NN, UK.
8Institute of Computational Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg 85764, Germany.
9Department of Computer Science, School of Computation, Information and Technology, Technical University of Munich, Garching 85748, Germany.
10Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
11Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
12German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg 20246, Germany.
13Department of Cardiovascular Surgery, University Heart & Vascular Center Hamburg-Eppendorf, Hamburg 20246, Germany.
14Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2B7, Canada.
15Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2B7, Canada.
16Medizinische Klinik und Poliklinik I, LMU Munich, Munich 81377, Germany.
17German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich 81377, Germany.
18Gene Center Munich, LMU Munich, Munich 81377, Germany.
19LMU Klinikum Munich, Munich 81377, Germany.
20Division of Cardiovascular Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
21Walter Brendle Centre of Experimental Medicine, University Hospital, Ludwig Maximilian University of Munich, Munich 81377, Germany.
22Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen 32545, Germany.
23British Heart Foundation Centre of Research Excellence, Imperial College London, London W12 0NN, UK.
24Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, UK.
25Precision Digital Health Unit of the Department of Internal Medicine III, Heidelberg University, Heidelberg 69120, Germany.
26Informatics for Life, Heidelberg 69120, Germany.
27German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg, Heidelberg 69120, Germany.
28Digital Health-Machine Learning Group, Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam 14482, Germany.
29Hasso Plattner Institute for Digital Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
30Department of Internal Medicine III, University of Heidelberg, Heidelberg 69120, Germany.
31Helmholtz-Institute for Translational AngioCardioScience (HI-TAC) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) at Heidelberg University, Heidelberg 69120, Germany.
32Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
33Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
34Charité-Universitätsmedizin Berlin, Berlin 10117, Germany.
Abstract
Hypertrophic cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, hypercontractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease, albeit with fewer adverse events. To investigate stage- and genotype-specific disease mechanisms, we performed single-nucleus RNA sequencing…
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