Dysferlin Deficiency May Lead to Heart Damage

MDA grantee Kevin Campbell at the University of Iowa in Iowa City, with colleagues at that institution and at the Medical College of Georgia in Augusta, has found that the protein dysferlin participates not only in repair of the membrane that surrounds each skeletal muscle fiber but also in an analogous membrane that surrounds each cardiac muscle cell. The report suggests that people with dysferlin-deficient muscle disorders may be prone to cardiac muscle damage.

A deficiency of dysferlin leads to either type 2B limb-girdle muscular dystrophy (LGMD 2B) or to Miyoshi distal muscular dystrophy, although the reasons for development of one condition or the other aren’t clear.

To date, cardiac muscle disease (cardiomyopathy) has not been considered part of human dysferlin deficiency, but the Campbell report in the July issue of the Journal of Clinical Investigation suggests that it may lead to this type of heart damage, especially when strenuous exercise is undertaken.

When the investigators studied dysferlin-deficient mice, they found the animals developed mild cardiomyopathy as they aged. Strenuous treadmill exercise worsened the damage in mice of the same age, and dysferlin deficiency accelerated development of cardiomyopathy in mice that also lacked the protein dystrophin. These dystrophin-deficient mice have fragile muscle fiber membranes and a disease resembling Duchenne muscular dystrophy.

The researchers write that patients with LGMD2B or Miyoshi distal MD may be predisposed to cardiac disease. Although they also note that, so far, only one such case has been reported.

In a related commentary in the same issue of the Journal of Clinical Investigation, Jan Lammerding and Richard Lee of Harvard Medical School in Boston note the recent identification of a family of  “ferlin” proteins that participate in cell membrane repair. They speculate that one of them, myoferlin, may be involved in repairing membranes surrounding each nucleus inside cardiac and skeletal muscle cells.

The authors note that understanding the balance of membrane injury and repair could provide insight into the great variability in different muscle diseases as well as lead to therapeutic strategies.

On Sept. 9, German researchers Katrin Wenzel and colleagues published a paper online in the Journal of Molecular Medicine showing that two out of seven patients they studied with LGMD 2B had signs and symptoms of cardiomyopathy, and an additional two showed some enlargement of the hear that may reflect an adaptive repair mechanism. The investigators recommend that people with LGMD be carefully evaluated for heart disease.