Limb-Girdle Muscular Dystrophy Type 1C

Abstract

LGMD type 1C has been recognized to be caused by mutations in the CAV3 gene, encoding for caveolin-3 protein. It is clinically characterized by mild to moderate muscle weakness, either distal or proximal, and exercise-induced muscle cramps. Caveolinopathy includes a series of different phenotypes. Muscle cramps following exercise are also a feature of rippling muscle disease which is induced by mechanical percussion or other stimulations and is due to caveolinopathy. Patients with high CK might have minimal muscle weakness. Other cases with dominant distal myopathy or isolated hyperCKemia have been described. Caveolin-3 is the muscle-specific member of the caveolin protein family, which is the principal component of the caveolae, small invaginations in the plasma membrane. Since immunohistochemistry with caveolin-3 antibody in muscle biopsy is a reliable tool for diagnosis, several such cases have been identified. The dominant inheritance implies that only one allele is mutated, and the reduction of the protein product is the consequent of a dominant-negative effect of gene mutations.