MULTIPLE INDEPENDENT MOLECULAR ETIOLOGY FOR LIMB-GIRDLE MUSCULAR-DYSTROPHY TYPE 2A PATIENTS FROM VARIOUS GEOGRAPHICAL ORIGINS

Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flank ing the LGMD2A locus and a search for CANP3 mutations were performed f or 21 LGMD2 pedigrees from various origins. In addition to the 16 muta tions described previously, we report 19 novel mutations. These data i ndicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support th e wide heterogeneity of molecular defects in this rare disease.