sarcoglycan

Sarcoglycans are a family of single-pass transmembrane glycoproteins that are part of the dystrophin-associated protein complex (DAPC) at the sarcolemma of skeletal and cardiac muscle. They help stabilize the connection between the cytoskeleton and the extracellular matrix during muscle contraction. The human sarcoglycan family includes alpha-sarcoglycan (SGCA), beta-sarcoglycan (SGCB), gamma-sarcoglycan (SGCG), and delta-sarcoglycan (SGCD); epsilon-sarcoglycan (SGCE) is expressed mainly in brain and other tissues. The four sarcoglycans form a subcomplex that associates with dystrophin and dystroglycan within the DAPC.

Mutations in SGCA, SGCB, SGCG, and SGCD cause autosomal recessive limb-girdle muscular dystrophy types 2D, 2E, 2C, and 2F, respectively, collectively known as sarcoglycanopathies. Clinically, patients present with progressive proximal muscle weakness and elevated serum creatine kinase, with onset from infancy to adulthood. Cardiomyopathy may occur in some subtypes. Pathophysiology involves loss or dysfunction of sarcoglycans, destabilizing the sarcolemmal DAPC and increasing membrane fragility, which leads to muscle fiber damage on contraction.

Diagnosis is based on genetic testing for SGCA/SGCB/SGCG/SGCD variants; immunohistochemistry of muscle biopsies may show reduced or absent sarcoglycan staining. Management is supportive, including physical therapy and respiratory and cardiac monitoring; there is no cure, though ongoing research explores gene therapy and other targeted approaches.

Animal and cellular models lacking sarcoglycan genes reproduce muscle pathology and are used to study mechanisms and test potential therapies.