Mutations in the dysferlin gene (2p13) have been recently identified as responsible for an autosomal recessive form of limb-girdle muscular dystrophy (LGMD), classified as LGMD2B. We describe three patients with dysferlinopathy showing different phenotypes. Two siblings, aged 24 and 21, had severe weakness and wasting in the muscles of the pelvic girdle and, to a lesser extent, of the shoulder girdle, and waddling gait. A 26-year-old woman had progressive difficulty walking by age 20.

more »

... n showed severe weakness and wasting of the lower limbs with distal predominance, and mild weakness in the upper limbs with pseudohypertrophy of the deltoid muscles. Muscle biopsy showed, in all patients, dystrophic changes. Immunohisto-chemical labelling for dysferlin on frozen sections and Western blot analysis showed absence of dysferlin band. Genetic studies for the identification of the mutation(s) are in progress. At least 14 LGMD genes have been mapped, including both autosomal dominant and autosomal recessive forms. On the other hand, discordant phenotypes may be seen in patients carrying the same mutation, even among affected siblings. Mutations in the dysferlin gene may manifest with mainly distal involvement (Miyoshi myopathy), or with classical clinical features of LGMD. Future knowledge of gene-protein function and protein interactions, and of modifying genes, will better clarify genotype-phenotype correlations in LGMD.