Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug?

dystrophin and to the sarcolemma at the COOH-terminal through its interaction with the oligomeric membrane complex known as the dystrophin-associated protein complex (DAPC), which includes the sarcoglycan (α , β, γ, δ, e) and dystroglycan (α , β) subcomplexes (9) (Figure 1). Interestingly, all of the known DCM-causing genes have been previously shown to cause skeletal myopathy, and mutations in the DAPC proteins are important causes of skeletal muscle disease (8, 10). Mouse models with defective sarcoglycan genes have all shown associated cardiomyopathy and skeletal myopathy (limb-girdle muscular dystrophy in mice and humans), while patients with sarcoglycan deficiency have associated DCM in about 30% of cases (11). In the δ-sarcoglycan‐deficient mouse, abnormalities of the coronary arteries were also found, resulting in ischemia (2). The mechanism has been speculated to be disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle. In contradistinction, patients with heterozygous δ-sarcoglycan mutations resulting in autosomal dominant DCM or sporadic DCM had normal coronary