How do genetic faults cause inherited heart muscle diseases?

Molecular mechanisms by which mutations in myofibrillar proteins cause primary cardiomyopathies (renewal)

Diseases of the heart muscle are called cardiomyopathies and can cause heart failure and sudden death, even in young people. Two of these conditions – hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) – are caused by faults in certain genes, which can be inherited through families. In HCM – which affects about one in 500 people – the heart muscle can thicken substantially whereas in DCM the heart enlarges and the muscle walls are thinner as a result. A great number of genetic faults – known as mutations – have been identified in HCM and DCM patients, the majority affecting the way the heart muscle contracts. Healthy hearts achieve their powerful pumping action through every heart muscle cell contracting in a coordinated pattern. The mutations that cause HCM and DCM tend to affect the proteins making up the structural components inside these cells that make it possible for them to contract. Even subtle changes in this process can have devastating consequences. In this research programme, three teams at Imperial College London will work together to investigate the problem from molecular-to-macro level. Their work will range from studying the way that mutations change the minute structure of individual molecules in the heart’s contraction apparatus, to studying the consequences this has on whole human hearts. The hope is that new findings from this research will inform the development of new ways to keep hearts healthy when they’re battling with a genetic mutation that can cause cardiomyopathy.