Clinical and Mechanistic Insights into the Genetics of Cardiomyopathy

• Type of Material: Article
• Authors: Michael Anthony Burke, Emory University; Stuart A. Cook, Imperial College London; Jonathan G. Seidman, Harvard Medical School; Christine E. Seidman, Harvard Medical School
• Language: English
• Date: 2016-12-27
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacc.2016.08.079
• Title of Journal or Parent Work: Journal of the American College of Cardiology
• ISSN: 0735-1097
• Volume: 68
• Issue: 25
• Start Page: 2871
• End Page: 2886
• Grant/Funding Information: This work was supported by: the Leducq Foundation Transatlantic Networks of Excellence (to Mr. Cook and Drs. J.G. and C.E. Seidman; the John S. LaDue Memorial Fellowship at Harvard Medical School, by the National Institutes of Health (Clinical Skills Development Core Training grant NHLBI #U10HL110337 to Dr. Burke; and grants NHLBI HL080494 and HL084553 to Drs. J.G. and C.E. Seidman; U01-HG006500: Seidman); and by the Howard Hughes Medical Institutes to Dr. C.E. Seidman.
• Keywords: genetic testing; COLLEGE-OF-CARDIOLOGY; BINDING-PROTEIN-C; LAMIN A/C GENE; HEAVY-CHAIN GENE; Cardiac & Cardiovascular Systems; RIGHT-VENTRICULAR CARDIOMYOPATHY; IDIOPATHIC RESTRICTIVE CARDIOMYOPATHY; molecular etiology; Life Sciences & Biomedicine; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; genetics; Science & Technology; hypertrophic cardiomyopathy; CARDIAC-TROPONIN-T; restrictive cardiomyopathy; AMERICAN-HEART-ASSOCIATION; Cardiovascular System & Cardiology; dilated cardiomyopathy
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

Over the last quarter-century, there has been tremendous progress in genetics research that has defined molecular causes for cardiomyopathies. More than a thousand mutations have been identified in many genes with varying ontologies, therein indicating the diverse molecules and pathways that cause hypertrophic, dilated, restrictive, and arrhythmogenic cardiomyopathies. Translation of this research to the clinic via genetic testing can precisely group affected patients according to molecular etiology, and identify individuals without evidence of disease who are at high risk for developing cardiomyopathy. These advances provide insights into the earliest manifestations of cardiomyopathy and help to define the molecular pathophysiological basis for cardiac remodeling. Although these efforts remain incomplete, new genomic technologies and analytic strategies provide unparalleled opportunities to fully explore the genetic architecture of cardiomyopathies. Such data hold the promise that mutation-specific pathophysiology will uncover novel therapeutic targets, and herald the beginning of precision therapy for cardiomyopathy patients.