[A patient with distal muscular dystrophy without mutations in dysferlin gene but with abnormal dysferlin localization in muscle fibers].

We report a 40-year-old man who noticed difficulty in standing on his tiptoe from approximately 36 years-old. He presented with selective calf muscle weakness on flexion. The serum creatine kinase (CK) level slightly increased to 569IU/l. Muscle computed tomography (CT) revealed selective gastrocnemius and soleus muscle atrophy with fat tissue replacement. A biopsy of the left gastrocnemius muscle revealed a marked variation in muscle fiber size and some necrotic and regenerating fibers. Immunohistochemical analysis using an anti-dysferlin antibody showed a faint and irregular immunostaining of the muscle surface membrane and abnormal immunoreactive depositions in the cytoplasm, although normal dysferlin content was detected by Western blotting. The sequence analysis of all exons of the dysferlin gene revealed no responsible mutations. The case had clinical and pathological findings similar to those of Miyoshi myopathy. The present study indicates that there may be a secondary abonormality of dysferlin derived from some other factors in patients with clinical and pathological findings similar to those of Miyoshi myopathy. The mechanism of dysferlin expression should be elucidated to obtain a conclusive pathogenetic mechanism underlying this disorder.