Myotubular myopathy (MTM) is an inherited neuromuscular disease caused by mutations in the MTM1 gene, which encodes the myotubularin protein. It is the most common and severe form of centronuclear myopathy, a type of inherited myopathy that causes problems with the tone and contraction of skeletal muscles. Symptoms of myotubular myopathy include muscle weakness and hypotonia (lack of muscle tone), noticeable at birth. Contractures (deformities caused by muscle weakening and shortening), may develop, particularly in the hips and knees. Spinal curvature (scoliosis) also may develop in childhood.
Myotubularin is a phosphatase enzyme required for normal muscle development.
Myotubularin, the protein encoded by the MTM gene, is an enzyme found in muscle. Its role is to remove chemical groups called phosphates from other proteins. Adding and removing phosphates is a key means of regulating the function of proteins. Experiments have suggested that myotubularin plays an important role in muscle development, maintenance, and contraction, although its exact role is still unknown. Disease-causing mutations in the MTM1 gene lead to a loss of function of the myotubularin protein.
MDA-supported scientists are developing gene therapy approaches for treatment of MTM. Protein replacement is also a focus of therapy development. Other potential strategies may develop from a detailed understanding of the function of the normal myotubularin protein, and the consequences of its loss.