title: Distal myopathy with rimmed vacuoles: impaired O-glycan formation in muscular glycoproteins.
abstract: Distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with early adult onset, displays distal dominant muscular involvement and is characterized by the presence of numerous rimmed vacuoles in the affected muscle fibers. The pathophysiology of DMRV has not been clarified yet, although the responsible gene was identified as that encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase involved in the biosynthesis of sialic acids. To identify defective carbohydrate moieties of muscular glycoproteins from DMRV patients, frozen skeletal muscle sections from seven patients with DMRV, as well as normal and pathological controls, were treated with or without sialidase or N-glycosidase F followed by lectin staining and lectin blotting analysis. The sialic acid contents of the O-glycans in the skeletal muscle specimens from the DMRV patients were also measured. We found that Arachis hypogaea agglutinin (PNA) lectin reacted strongly with sarcolemmal glycoproteins in the DMRV patients but not with those in control subjects. alpha-Dystroglycan from the DMRV patients strongly associated with PNA lectin, although that from controls did not. The sialic acid level of the O-glycans in the DMRV muscular glycoproteins with molecular weights of 30 to 200 kd was reduced to 60 to 80% of the control level. The results show that impaired sialyl O-glycan formation in muscular glycoproteins, including alpha-dystroglycan, occurs in DMRV.
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Tajima
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Uyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Go
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sato
authors.forename: Nodoka
authors.initials: N
authors.lastname: Tao
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kotani
authors.forename: Hirotake
authors.initials: H
authors.lastname: Hino
authors.forename: Akemi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sanai
authors.forename: Ken
authors.initials: K
authors.lastname: Kitajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D049310:Distal Myopathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D006026:Glycoside Hydrolases; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D011134:Polysaccharides / Q000378:metabolism*; D014617:Vacuoles / Q000473:pathology
chemical_list: D006023:Glycoproteins; D037102:Lectins; D011134:Polysaccharides; D006026:Glycoside Hydrolases