DYSF

The DYSF gene provides instructions for making a protein called dysferlin. The specific function of this protein is not well understood. It is believed to be involved in repairing damage to muscle cells. It may help fuse gaps in muscle cell membranes by interacting with other molecules, including proteins called calpain-3 and caveolin-3. Researchers suggest that dysferlin may also be involved in the maturation of new muscle fibers (regeneration).

limb-girdle muscular dystrophy - caused by mutations in the DYSF gene

More than 300 mutations in the DYSF gene that can cause limb-girdle muscular dystrophy type 2B have been identified. Limb-girdle muscular dystrophy is a group of related disorders characterized by muscle weakness and wasting, particularly in the shoulders, hips, thighs, and upper arms. Muscle problems caused by DYSF gene mutations, such as limb-girdle muscular dystrophy type 2B, are called dysferlinopathies.

DYSF gene mutations may disrupt the function of the dysferlin protein, interfering with the muscle repair process. Studies suggest that inefficient repair of damaged muscle fibers may lead to inflammation and degeneration of muscles, resulting in muscle weakness.

other disorders - caused by mutations in the DYSF gene

DYSF gene mutations also cause other dysferlinopathies called Miyoshi distal myopathy and distal myopathy with anterior tibial onset. In contrast with limb-girdle muscular dystrophy, in which muscle weakness is most severe in the muscles close to the center of the body (proximal muscles), the muscle weakness in these dysferlinopathies is more severe in muscles farther from the center of the body (distal muscles). In Miyoshi distal myopathy and distal myopathy with anterior tibial onset, the effects are most apparent in the muscles of the lower legs.

Miyoshi distal myopathy involves calf muscle weakness, which may make it difficult to stand on tiptoe. The muscle weakness in Miyoshi distal myopathy progresses slowly; it may eventually affect the thighs and cause difficulty walking. Some researchers consider Miyoshi distal myopathy to be a variant of limb-girdle muscular dystrophy rather than a separate disorder.

Distal myopathy with anterior tibial onset first becomes apparent in a muscle called tibialis anterior, which is located at the front of the lower leg and is involved in flexing the foot. This dysferlinopathy progresses more quickly to muscles of the upper leg than does Miyoshi distal myopathy, and affected individuals eventually require wheelchair assistance.