Limb-girdle muscular dystrophy: one gene with different phenotypes, one phenotype with different genes

Abstract

Among 14 limb-girdle muscular dystrophy genes that have been mapped, 10 (three autosomal dominant and seven autosomal recessive) have so far had their product identified. This review will focus on the most recent data in the field and on our own experience of more than 200 patients studied with autosomal recessive-limb-girdle muscular dystrophy, classified from calpainopathy to telethoninopathy. Genotype: phenotype correlations in this highly heterogeneous group show a similar clinical course among patients with different forms, whereas a discordant phenotype may be seen in unrelated patients or in affected sibs carrying the same mutation. Understanding such similarities or differences remains a major challenge. It will depend on future knowledge of gene-protein functions, on protein interactions and on identifying modifying genes and other factors underlying clinical variability.