Advances in molecular genetics have led to the identification of mutations in each troponin subunit that cause different human cardiomyopathies. Mutations in the genes for cardiac troponin T (CTnT), troponin I (CTnI), and troponin C (CTnC) cause familial hypertrophic cardiomyopathy (FHC) and are associated with varying prognosis and mild-to-moderate hypertrophy. Mutations in CTnT and CTnC can also cause dilated cardiomyopathy (DCM), whereas mutations in CTnI can cause restrictive cardiomyopathy (RCM). All together, 60 mutations have so far been found in troponin subunits associated with cardiomyopathy. Recently, multiple cardiomyopathic phenotypes (either HCM or RCM), arising from a single nucleotide mutation in the same codon of CTnI, R145, have been documented. Although the clinical phenotypes of the cardiomyopathies vary, two common features are present in most cardiomyopathy patients: altered Ca2+ sensitivity of force development and impaired energy metabolism. Here, we present the analyses of how these troponin mutations affect the in vitro contractile protein function and the hypotheses derived to explain the development of these disease states.
- Dilated cardiomyopathy
- Familial hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)