Membrane protein kinase alteration in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DuD) is the severe form of heredo familial muscular dystrophy inherited as a sex linked recessive trait. The primary clinical manifestations are progressive muscle weakness usually starting in the pelvic girdle accompanied by hypertrophy in the calf musculature. Significant cardiac abnormalities and mental retardation have also been reported. The primary inherited metabolic defect is unknown. Elevated levels of muscle enzyme activities in the serum and their depletion in the muscle tissue have, however, long pointed to an abnormality in the plasma membrane as the probable site of the genetic defect. To explore potential membrane alterations in DuD the authors used a strategy which had been successful in another common form of hereditary familial myopathy, myotonic muscular dystrophy (MyD). Changes of denervation, atrophy, fatty infiltration, or fibrosis may make muscle membrane alterations impossible to interpret unless correlated with similar changes in other tissues. Therefore red cell membranes were used to explore the membrane abnormality in studies of MyD. MyD red cell ghost phospholipids, polypeptides, and carbohydrates were similar to age and sex matched controls. Endogenous protein phosphorylation, however, was decreased in fresh as well as frozen red blood cell membranes derived from patients with MyD.