When clinically distinct diseases turn out to be caused by defects in the same cellular process, new ideas about pathophysiology and about avenues for therapeutic intervention can rapidly emerge. That is exactly what has happened in a study of a congenital heart defect called dilated cardiomyopathy, recently published in the New England Journal of Medicine.

Dilated cardiomyopathy affects 1 in every 2,500 individuals, and causes early-onset heart failure. It is often associated with other phenotypes, such as skeletal-muscle defects, but Kamisago et al. focused on a large family with autosomal dominant dilated cardiomyopathy in the absence of other clinical symptoms. Linkage analysis led the authors to the cardiac β-myosin heavy chain ( MYH7 ) gene and, indeed, the same missense mutation was found in all affected individuals in this family. A second mutation in MYH7 was discovered by screening a further 20 families. Following this lead, the authors tested other candidate genes involved in the sarcomere — the basic contractile unit in striated muscle — and found one more mutation in a critical region of the troponin T gene ( TNNT2 ). Troponin T regulates the interaction between myosin and actin. On the basis of the known structural properties of the residues that are mutated in TNNT2 and MYH7, Kamisago et al. predict that all three mutations will impair the contractile function of cardiac muscle.

Mutations in MYH7 and TNNT2 have previously been found in hypertrophic cardiomyopathy, the pathology of which is quite different from dilated cardiomyopathy. Functional studies of some of the hypertrophic cardiomyopathy mutations indicate that they might enhance, rather than impair, the contractile function of cardiac muscle.

Overall, defects in a single cellular component — the cardiac sarcomere — appear to unite two distinct pathologies. The implication is that sarcomere abnormalities will be a more common cause of cardiac dysfunction than previously suspected, and that the sarcomere is therefore an attractive target at which to aim new ideas about therapeutic intervention.