α-Dystroglycan does not play a major pathogenic role in autosomal recessive hereditary inclusion-body myopathy

Mutations of the GNE gene are responsible for autosomal recessive hereditary inclusion-body myopathy (HIBM). In this study we searched for the presence of any significant abnormality of α-dystroglycan (α-DG), a highly glycosylated component of the dystrophin-glycoprotein complex, in 5 HIBM patients which were previously clinically and genetically characterized. Immunocytochemical and immunoblot analysis showed that α-DG extracted from muscle biopsies was normally expressed and displayed its typical molecular mass. Immunoblot analysis on the wheat germ lectin-enriched glycoprotein fraction of muscles and primary myotubes showed a reduced amount of α-DG in 4 out of 5 HIBM patients, compared to normal and other diseased muscles. However, such altered lectin-binding behaviour, possibly reflecting a partial hyposialylation of α-DG, did not affect the laminin binding properties of α-DG. Therefore, the subtle changes within the α-DG glycosylation pattern, detected in HIBM muscles, likely do not play a key pathogenic role in this disorder.