Personalized Medicine: Genetic Diagnosis for Inherited Cardiomyopathies/Channelopathies
ABSTRACT Major advances in the field of molecular genetics have expanded our ability to identify genetic substrates underlying the pathogenesis of various disorders that follow Mendelian inheritance patterns. Included among these disorders are the potentially lethal and heritable channelopathies and cardiomyopathies for which the underlying genetic basis has been identified and is now better understood. Clinical and genetic heterogeneity are hallmark features of these disorders, with thousands of gene mutations being implicated within these divergent cardiovascular diseases. Genetic testing for several of these heritable channelopathies and cardiomyopathies has matured from discovery to research-based genetic testing to clinically/commercially available diagnostic tests. The purpose of this review is to provide the reader with a basic understanding of human medical genetics and genetic testing in the context of cardiovascular diseases of the heart. We review the state of clinical genetic testing for the more common channelopathies and cardiomyopathies, discuss some of the pertinent issues that arise from genetic testing, and discuss the future of personalized medicine in cardiovascular disease. Full English text available from:www.revespcardiol.org/en.
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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 the 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 HCM 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. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
Revista Espanola de Cardiologia 02/2014; 67(2):148-50. DOI:10.1016/j.rec.2013.07.006 · 3.34 Impact Factor
Revista Espanola de Cardiologia 03/2014; 67(3):229-31. DOI:10.1016/j.rec.2013.09.020 · 3.34 Impact Factor