title: Genetic advances in sarcomeric cardiomyopathies: state of the art.
abstract: Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine.
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA cho@partners.org.
authors: Carolyn Y
authors: CY
authors: Ho
authors: Centre de référence maladies cardiaques héréditaires, ICAN, Inserm UMR_1166, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France Université de Versailles-Saint Quentin, Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France.
authors: Philippe
authors: P
authors: Charron
authors: Centre de référence maladies cardiaques héréditaires, ICAN, Inserm UMR_1166, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
authors: Pascale
authors: P
authors: Richard
authors: Genetic Diagnostic Unit, Careggi University Hospital, Florence, Italy.
authors: Francesca
authors: F
authors: Girolami
authors: Department of Clinical Genetics, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
authors: Karin Y
authors: KY
authors: Van Spaendonck-Zwarts
authors: Department of Cardiology, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
authors: Yigal
authors: Y
authors: Pinto
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology
chemical_list: D005819:Genetic Markers
keywords: Dilated cardiomyopathy; Genetics; Hypertrophic cardiomyopathy; Next Generation Sequencing; Sarcomere
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