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

Hereditary rippling muscle disease (RMD) is an autosomal dominant human dis order characterized by mechanically triggered contractions of skeletal musc le(1-4). Genome-wide linkage analysis has identified an RMD locus on chromo some 3p25. We found missense mutations in positional candidate CAM (encodin g 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.