Extracellular matrix-driven congenital muscular dystrophies.

Skeletal muscle function relies on the myofibrillar apparatus inside myofibers as well as an intact extracellular matrix surrounding each myofiber. Muscle extracellular matrix (ECM) plays several roles including but not limited to force transmission, regulation of growth factors and inflammatory responses, and influencing muscle stem cell (i.e. satellite cell) proliferation and differentiation. In most myopathies, muscle ECM undergoes remodeling and fibrotic changes that may be maladaptive for normal muscle function and recovery. In addition, mutations in skeletal muscle ECM and basement proteins can cause muscle disease. In this review, we summarize the clinical features of two of the most common congenital muscular dystrophies, COL6-related dystrophies and LAMA2-related dystrophies, which are caused by mutations in muscle ECM and basement membrane proteins. The study of clinical features of these diseases has helped to inform basic research and understanding of the biology of muscle ECM. In return, basic studies of muscle ECM have provided the conceptual framework to develop therapeutic interventions for these and other similar disorders of muscle.