Sarcomeric-encoding genes Clause Samples

Sarcomeric-encoding genes. The sarcomere, composed of thick and thin filaments in addition to the giant protein titin, makes up the basic contractile unit of cardiac muscle and is directly responsible for the mechanics of force generation and propagation (154). Mutations of the genes encoding thick and thin filaments are well-described for HCM, as are those affecting TTN for DCM. However, some sarcomere-encoding genes such as MYH7, and genes regulating sarcomeric contraction –TNNT2 and TNNC1 can be affected by private or rare variants that run uniquely within families (155). The age of presentation due to these non-titin variants appears to be widely variable, with more severe disease occurring in younger life and more subtle dysfunction occurring in adulthood, with a small subset characterised by a higher incidence of major arrhythmic events and heart failure outcomes after the age of fifty (61,155–157).