Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1963-1969 |
Number of pages | 7 |
Journal | Human molecular genetics |
Volume | 5 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1996 |
Funding
We are extremely grateful to Dr Ivo Pavanello Filho, for the procedure of muscle biopsies, to Ana Beatriz A. Vieira, for muscle and functional assessment of patients, to Cleber S. Costa, Simone Campioto, Antonia M. P. Cerqueira and Constancia Urbani for their invaluable collaboration. This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desen-volvimento Científico e Tecnológico (CNPq), PADCT, International Agency of Atomic Energy, Telethon-Italy, Associação Brasileira de Distrofia Muscular (ABDIM). E.M.M is supported by NIH HL03448. L.M.K. is an investigator of the Howard Hughes Medical Institute and is supported by NIH NS23740.
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Molecular Biology