What are the genetic changes related to familial hypertrophic cardiomyopathy ?
Mutations in one of several genes can cause familial hypertrophic cardiomyopathy; the most commonly involved genes are MYH7, MYBPC3, TNNT2, and TNNI3. Other genes, including some that have not been identified, may also be involved in this condition.  The proteins produced from the genes associated with familial hypertrophic cardiomyopathy play important roles in contraction of the heart muscle by forming muscle cell structures called sarcomeres. Sarcomeres, which are the basic units of muscle contraction, are made up of thick and thin protein filaments. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body.  The protein produced from the MYH7 gene, called cardiac beta ()-myosin heavy chain, is the major component of the thick filament in sarcomeres. The protein produced from the MYBPC3 gene, cardiac myosin binding protein C, associates with the thick filament, providing structural support and helping to regulate muscle contractions.  The TNNT2 and TNNI3 genes provide instructions for making cardiac troponin T and cardiac troponin I, respectively, which are two of the three proteins that make up the troponin protein complex found in cardiac muscle cells. The troponin complex associates with the thin filament of sarcomeres. It controls muscle contraction and relaxation by regulating the interaction of the thick and thin filaments.  It is unknown how mutations in sarcomere-related genes lead to hypertrophy of the heart muscle and problems with heart rhythm. The mutations may result in an altered sarcomere protein or reduce the amount of the protein. An abnormality in or shortage of any one of these proteins may impair the function of the sarcomere, disrupting normal cardiac muscle contraction. Research shows that, in affected individuals, contraction and relaxation of the heart muscle is abnormal, even before hypertrophy develops. However, it is not clear how these contraction problems are related to hypertrophy or the symptoms of familial hypertrophic cardiomyopathy.