The sarcomere is the principal contractile unit of striated muscle. Mutations in genes encoding sarcomeric proteins are responsible for a range of diseases including hypertrophic, dilated and restrictive cardiomyopathies and ventricular non-compaction. The downstream molecular pathways leading to these heterogeneous phenotypes include changes in acto-myosin cross-bridge kinetics, altered mechanosensation, disturbed calcium sensitivity, de-regulated signalling pathways, inefficient energetics, myocardial ischaemia and fibrosis. The elucidation of the genetic causes of cardiomyopathy has helped in understanding the structure and function of the sarcomere and a more detailed knowledge of the sarcomere and its associated proteins has suggested additional gene candidates. The new hope is that these advances will stimulate the discovery of disease-modifying drugs.
Keywords: GENETICS; MYOCARDIAL DISEASE.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.