Reviews of Translational Medicine and Genomics in Cardiovascular Disease: New Disease Taxonomy and Therapeutic Implications: Cardiomyopathies: Therapeutics Based on Molecular Phenotype

摘要: The enduring subdivision of cardiomyopathies into hypertrophic (HCM), dilated (DCM), and restrictive (RCM) categories reflects the emphasis traditional classifications on morphology. Rapid advances in genetic interrogation these disorders have redefined their taxonomy revealed potential conflicts between old new classifications. Hypertrophic cardiomyopathy has been as a disease perturbed sarcomere function. Dilated is that results from more varied perturbations, including, but not limited to, defects cytoskeleton. Positional cloning candidate gene approaches successful identifying >40 loci, many which led to genes HCM, DCM, RCM, arrhythmogenic right ventricular cardiomyopathy. These findings provide mechanistic insights, permit screening, extent, facilitate prognostication. Although single analyses rapidly focus down underlying pathways, they do take account all relevant variation human genome. Correspondingly, genomics, through microarrays, facilitated characterization broader downstream elements. As well refining taxonomic reclassification cardiomyopathies, genomic approaches, coupled with functional studies, identified novel therapeutic targets, such cardiac energetics, calcium handling, apoptosis. We review successes pitfalls impact current future clinical care.