THE SARCOGLYCAN COMPLEX IN THE 6 AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR-DYSTROPHIES

To enhance our understanding of the autosomal recessive limb-girdle mu scular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (alpha-, beta-, gamma-, delta-SG), dystrophin, be ta-dystroglycan (beta-DG) and merosin, All patients with LGMD2A and 2B had a mild clinical course while those with a primary sarcoglycan mut ation (LGMD2C to 2F) had a range of clinical severity, Dystrophin and merosin immunofluorescence pattern was positive in patients with all s ix AR LGMDs. The majority of patients with a severe Duchenne-like phen otype presented total absence of the SG complex, However, some excepti ons were found in 13q linked patients, indicating that the presence of a certain labelling for components of the SG may not be prognostic fo r a milder phenotype, The observation that the primary absence of alph a-SG results in the total absence of beta- and delta-SG but not of gam ma-SG suggests that the alpha-, beta- and delta-subunits of sarcoglyca n 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 beta-, gamma- and delta-SG de ficiencies, In contrast, beta-DG staining was retained in all patients , suggesting that the association between SG and DG subcomplexes is no t so strong. Based on the above findings, we have refined the model fo r the interaction among the known glycoproteins of the sarcoglycan com plex, within the DGC.