Molecular genetic analysis of dysferlin in Japanese patients with Miyoshi myopathy

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy f irst described by Miyoshi in 1967. MM is caused by mutations of a dysferlin gene (DYSF) at chromosome 2p13. We identified 8 novel mutations and 3 poly morphisms in the DYSF among seven unrelated Japanese families. The mutation s in our MM occurred throughout the DYSF and showed no mutational hot spot. Expression of dysferlin at the plasma membrane of skeletal muscle was defi cient in all the patients studied. In two families, we found two distinct c linical phenotypes (distal and proximal dominancies) within a family. This is the first report of DYSF mutations and dysferlin deficiency in Japanese patients with MM. Our findings suggest, (1) the specific deficiency of dysf erlin at the plasma membrane of skeletal muscle in MM, (2) the ethnic diffe rence in DYSF mutations and (3) the presence of possible genetic or environ mental modification factors which influence the clinical variability of MM.