Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by myocardial wall thickening (almost always confined to the left ventricle). In humans HCM is a genetic disease and is usually inherited in an autosomal dominant pattern.The first mutation (in the P-myosin heavy chain gene [|3-MHC]) responsible for HCM in humans was identified in 1989 and since then over 600 mutations in 10 genes that encode for sarcomeric proteins have been identified in human families with HCM. They include the p-myosin heavy chain, a-tropomyosin, cardiac troponins I, C, and T, myosin binding protein C, essential and regulatory light chains, titin, and actin genes. The genes with the most mutations described and the ones that most commonly produce disease are the P-MHC and cardiac myosin binding protein C (MYBPC3) genes, which account for roughly 60% of the mutations identified and for 60% of HCM cases. It is now known that sarcomeric gene mutations actually cause HCM since several mutations that have been identified in human families with HCM have been placed in transgenic mice and the disease reproduced (at least partially), thus fulfilling Koch's postulates.11"1'A minority of HCM cases in humans are caused by mutations in non sarcomeric genes. These include the gene that codes for LIM protein and the gene coding for AMP-activated kinase. The latter produces glycogen accumulation in the myocardium that mimics HCM. Interestingly mutations in P-myosin heavy chain, a-tropomyosin, titin, and troponin T genes also cause dilated and restrictive cardiomyopathies along with left ventricular noncompaction. Mutations in the LIM protein gene also cause DCM in mice.However, the mutations that cause other forms of cardiomyopathy are at different sites on these genes than those that cause HCM.
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