Positional cloning of the gene for Miyoshi myopathy and limb-girdle muscular dystrophy

Miyoshi myopathy (MM) is autosomal recessive distal muscular dystrophy that we have mapped to chromosome 2 p13. We constructed a 3 Mb P 1 -derived artificial chromosome contig spanning the MM candidate region. Using this and new polymorphic markers within it, we recently identified a novel, full- length 6.9 kb muscle cDNA, whose corresponding protein we designated 'dysferlin' (Nature Genet, 1998: 20: 31-36). We described eighteen mutations in the dysferlin gene with MM or limb-girdle muscular dystrophy type 2 B (LGMD 2 B). Most are predicted to block translation of dysferlin protein. In some cases, corresponding Western immunoblotting reveals absence of dysferlin in muscle biopsies. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb-girdle dystrophy, distal myopathy with anterior tibial onset).