Genetic Cardiomyopathies Causing Heart Failure
- 30 August 2013
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 113 (6), 660-675
- https://doi.org/10.1161/circresaha.113.300282
Abstract
Despite the striking advances in medical and surgical therapy, the morbidity, mortality, and economic burden of heart failure (HF) remain unacceptably high. There is increasing evidence that the risk and course of HF depend on genetic predisposition; however, the genetic contribution to HF is heterogeneous and complex. At one end of the spectrum are the familial monogenic HF syndromes in which causative mutations are rare but highly penetrant. At the other, HF susceptibility and course may be influenced by more common, less penetrant genetic variants. As detailed in this review, efforts to unravel the basis of the familial cardiomyopathies at the mendelian end of the spectrum already have begun to deliver on the promise of informative mechanisms, novel gene-based diagnostics, and therapies for distinct subtypes of HF. However, continued progress requires the differentiation of pathogenic mutations, disease modifiers, and rare, benign variants in the deluge of data emerging from increasingly accessible novel sequencing technologies. This represents a significant challenge and demands a sustained effort in analysis of extended family pedigrees, diligent clinical phenotyping, and systematic annotation of human genetic variationKeywords
This publication has 100 references indexed in Scilit:
- RBM20, a gene for hereditary cardiomyopathy, regulates titin splicingNature Medicine, 2012
- Truncations of Titin Causing Dilated CardiomyopathyThe New England Journal of Medicine, 2012
- Furthering the link between the sarcomere and primary cardiomyopathies: Restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathyAmerican Journal of Medical Genetics Part A, 2011
- Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) StudiesAmerican Heart Journal, 2010
- Compound and Digenic Heterozygosity Contributes to Arrhythmogenic Right Ventricular CardiomyopathyJournal of the American College of Cardiology, 2010
- ANKRD1, the Gene Encoding Cardiac Ankyrin Repeat Protein, Is a Novel Dilated Cardiomyopathy GeneJournal of the American College of Cardiology, 2009
- Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Is a Fully Penetrant, Lethal Arrhythmic Disorder Caused by a Missense Mutation in the TMEM43 GeneAmerican Journal of Human Genetics, 2008
- A Novel Dominant Mutation in Plakoglobin Causes Arrhythmogenic Right Ventricular CardiomyopathyAmerican Journal of Human Genetics, 2007
- Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Associated with Mutations in the Desmosomal Gene Desmocollin-2American Journal of Human Genetics, 2006
- DSG2 Mutations Contribute to Arrhythmogenic Right Ventricular Dysplasia/CardiomyopathyAmerican Journal of Human Genetics, 2006