The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies

To enhance our understanding of the autosomal recessive limb-girdle muscular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (α-, β-, γ-, δ-SC), dystrophin, β-dystroglycan (β-DG) and merosin. All patients with LGMD2A and 2B had a mild clinical course while those with a primary sarcoglycan mutation (LGMD2C to 2F) had a range of clinical severity. Dystrophin and merosin immunofluorescence pattern was positive in patients with all six AR LGMDs. The majority of patients with a severe Duchenne-like phenotype presented total absence of the SG complex. However, some exceptions were found in 13q linked patients, indicating that the presence of a certain labelling for components of the SG may not be prognostic for a milder phenotype. The observation that the primary absence of α-SG results in the total absence of β- and δ-SG but not of γ-SG suggests that the α-, β- and δ-subunits of sarcoglycan may be more closely associated. A secondary reduction in dystrophin amount was seen in patients with primary sarcoglycan mutations, which was most marked in patients with primary β-, γ- and δ-SG deficiencies. In contrast, β-DG staining was retained in all patients, suggesting that the association between SG and DG subcomplexes is not so strong. Based on the above findings, we have refined the model for the interaction among the known glycoproteins of the sarcoglycan complex, within the DGC.