Objective: To clarify the expression patterns of dysferlin in limb-girdle muscular dystrophy (LGMD) and Miyoshi myopathy (MM), and to investigate the frequency and clinicopathologic features of dysferlinopathy.
Methods: The expressing patterns of dysferlin were analyzed by immunohistochemistry, with a set of antibodies against dystrophin, alpha-sarcoglycan and dysferlin, in the biopsied muscle specimens from 45 patients with LGMD or MM diagnosed on the basis of clinical manifestations and muscle pathological features. The specimens with abnormal dysferlin expression shown by IHC were further analyzed with Western blotting for a quantitative evaluation.
Results: Eight patients were proved to be primary dysferlinopathy according to total dysferlin deficiency or a significant decrease of dysferlin (less than 15% that of normal value). The clinical manifestations of 5 of the 8 dysferlinopathy patients were consistent with those of typical MM, and the other 3 were diagnosed as with LGMD. All patients had an average onset at the age of 18.8 years. Two of them had family history, and one patient had consanguineous mating parents, meaning an autosomal recessive inheritance pattern. The serum CK levels were 6240 IU/L on average. EMG showed myogenic patterns in all patients. Muscular pathology showed typical changes of muscular dystrophy in all patients. Focal or scattered inflammatory cellular infiltrations were found in 3 cases.
Conclusion: The clinical and pathological features of dysferlinopathy are nonspecific. Inflammatory cellular infiltrations are relatively common in biopsied muscles of dysferlinopathy patients, which may cause misdiagnosis of inflammatory myopathy. Identification of dysferlin expression by IHC and Western blotting are essential for the diagnosis of dysferlinopathy and differential diagnosis of inflammatory myopathy.