Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle(1-4). Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAM (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAM have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases.