Phenotypic plasticity of sarcomeric protein mutations.

he practice of medicine today is founded primarily on the henotypic characteristics of diseases. The recognition of ommon forms of cardiomyopathies as hypertrophic, diated, restrictive, and arrhythmogenic right ventricular cariomyopathies typifies the phenotype-based approach to iseases. The approach clearly has had numerous positive mpacts on the diagnosis, prognostication, prevention, and reatment of various diseases. The advent of the betalockers and inhibitors of the renin-angiotensin-aldosterone athway in the treatment of systolic heart failure are estaments to the clinical utility of the phenotype-based pproach. Despite the enormous impacts, however, the henotype-based approach has considerable shortcomings. or example, the approach has failed to offer a cure for many iseases including systolic heart failure, in which pharmaologic interventions reduce mortality by approximately 0% to 30% and prolong survival by a few months (1–3).