What is Miyoshi Myopathy?

Miyoshi myopathy is a form of muscle degeneration or muscular dystrophy that begins in young adults, causing progressive muscle weakness. This usually begins in the distal, posterior leg muscles. In some cases, the disease begins in the proximal leg muscles, in which case it is designated limb-girdle dystrophy (type 2B). One hallmark of the disease is release into the bloodstream of high levels of enzymes that normally reside only inside muscle cells. The diagnosis is established by a combination of studies including the clinical evaluation, a muscle biopsy, DNA tests, and an electrical test known as an electromyogram or EMG. There is presently no primary treatment for Miyoshi myopathy although some symptomatic measures may be beneficial.

The cause of Mishoshi myopathy and limb girdle muscular dystrophy 2B is deficiency of a skeletal muscle protein known as dysferlin. This protein was identified by members of the Day Lab and collaborators in 1998. The dysferlin gene is relatively large and complex, comprising 55 exons (protein templates) that encode the 237 kDa dysferlin protein. The dysferlin protein is localized to the membrane of muscle cells. However, the normal physiological function of dysferlin is unknown and it is not clear how its absence causes myofiber degeneration.

Miyoshi Myopathy Research Programs at the MGH

The research program in Miyoshi myopathy has several components. (1) We are screening for new mutations in the dysferlin gene in Miyoshi and LGMD-2B patients. (2) We are generating a new mouse model of Miyoshi myopathy. (3) Studies are in progress to identify patterns of genes that are turned on or off at different stages of Miyoshi myopathy (using cDNA gene arrays). (4) We are actively studying possible treatment strategies in Miyoshi myopathy mice. (5) We have also studied improved diagnostic testing for the dysferlin protein using a simple blood test.