Commentary can cause DCM and cleaves dystrophin, thereby impairing the function of dystrophin and its associated glycoproteins (6). Mutations in the intermediate filament protein, nuclear lamin (lamin A/C), and a novel nuclear membrane–associated protein, emerin, can result in Emery-Dreifuss muscular dystrophy that can be associated with DCM (3). Another disease gene identified for DCM is α-cardiac actin (7), which has been regarded as a component of the sarcomere, although more recent evidence suggests it may play an important role in the intrasarcomeric cytoskeleton as well (see further discussion below). In addition to these identified loci, linkage studies have defined 7 different DCM loci but the specific genes remain to be identified (2, 3).

In a previous issue of the JCI, work by Mogensen et al.(8) suggests that a mutation within the α-cardiac actin gene may also result in HCM. This is of particular interest, as it is the first report of mutations within the same cytoskeletal gene causing either HCM or DCM in humans. It has been speculated that mutations in proteins that directly affect sarcomeric contractile function will eventually result in HCM. On the other hand, mutations in