GNE protein expression and subcellular distribution are unaltered in HIBM

Neurology. 2007 Aug 14;69(7):655-9. doi: 10.1212/01.wnl.0000267426.97138.fd.

Abstract

Mutations in GNE encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) cause hereditary inclusion body myopathy (HIBM). To define the role of GNE mutations in HIBM pathogenesis, GNE protein expression was analyzed. GNE protein is expressed at equal levels in HIBM patients and normal control subjects. Immunofluorescence detection of GNE did not reveal any mislocalization of GNE in skeletal muscle. We conclude that impaired GNE function, not lack of expression, may be the key pathogenic factor in HIBM. For diagnostic purposes, direct genetic analysis of the GNE gene in patients with IBM will remain the mainstay and is not aided by immunohistochemistry or immunoblotting using antibodies against the GNE protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbohydrate Epimerases / biosynthesis
  • Carbohydrate Epimerases / genetics
  • Cell Line
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Male
  • Multienzyme Complexes / biosynthesis*
  • Multienzyme Complexes / genetics*
  • Mutation
  • Myositis, Inclusion Body / enzymology*
  • Myositis, Inclusion Body / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / biosynthesis
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Subcellular Fractions / enzymology

Substances

  • Multienzyme Complexes
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
  • Phosphotransferases (Alcohol Group Acceptor)
  • N-acylmannosamine kinase
  • Carbohydrate Epimerases
  • UDP acetylglucosamine-2-epimerase