Tropomyosin and dilated cardiomyopathy: revenge of the actinomyosin "gatekeeper".

s e f o ne of the most important recent advances in our undertanding of the basic mechanisms of genetic cardiac disease as been the central role played by mutations in structural roteins. Nearly 2 decades ago Geisterfer-Lowrance et al. 1) published the first linkage of a mutation in the betayHC gene to hypertrophic cardiomyopathy (HCM). Since hat seminal finding, mutations in a broad array of proteins hat contribute to the structural and functional integrity of omponents of the cardiac sarcomere, myocellular cytoskelton, and the sarcolemma have been definitively linked to a ast range of clinical cardiomyopathies (2). Sarcomeric rotein mutations represent a particularly intriguing subset f the genetic cardiomyopathies in that independent mutaions within the same gene and often within the same unctional domain can cause widely divergent, clinically elevant patterns of pathogenic ventricular remodeling.