alpha-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 alpha-dystroglycan (alpha-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 alpha-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 alpha-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 alpha-DG, did not affect the laminin binding properties of alpha-DG. Therefore, the subtle changes within the alpha-DG glycosylation pattern, detected in HIBM muscles, likely do not play a key pathogenic role in this disorder.
Broccolini
Aldobrando
A
Department of Neuroscience, Catholic University, L.go A. Gemelli 8, 00168 Rome, Italy.
Gliubizzi
Carla
C
Pavoni
Ernesto
E
Gidaro
Teresa
T
Morosetti
Roberta
R
Sciandra
Francesca
F
Giardina
Bruno
B
Tonali
Pietro
P
Ricci
Enzo
E
Brancaccio
Andrea
A
Mirabella
Massimiliano
M
D000328:Adult; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000151:congenital* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D007797:Laminin; D049030:Dystroglycans