No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation (2005)

Author(s): Salama I, Hinderlich S, Shlomai Z, Eisenberg I, Krause S, Yarema K, Argov Z, Lochmuller H, Reutter W, Dabby R, Sadeh M, Ben-Bassat H, Mitrani-Rosenbaum S

    Abstract: Hereditary inclusion body myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult-onset, slowly progressive distal and proximal muscle weakness, which is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme in the biosynthetic pathway of sialic acid. In order to investigate the consequences of the mutated GNE enzyme in muscle cells, we have established cell cultures from muscle biopsies carrying either kinase or epimerase mutations. While all myoblasts carrying a mutated GNE gene show a reduction in their epimerase activity, only the cells derived from the patient carrying a homozygous epimerase mutation present also a significant reduction in the overall membrane bound sialic acid. These results indicate that although mutations in each of the two GNE domains result in an impaired enzymatic activity and the same HIBM phenotype, they do not equally affect the overall sialylation of muscle cells. This lack of correlation suggests that the pathological mechanism of the disease may not be linked solely to the well-characterized sialic acid pathway.

      • Date: 04-03-2005
      • Journal: Biochemical and Biophysical Research Communications
      • Volume: 328
      • Issue: 1
      • Pages: 221-226
      • Publisher: Academic Press
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Cell Membrane/ metabolism Cells, Cultured Humans Metabolism, Inborn Errors/genetics/metabolism Multienzyme Complexes/ genetics/ metabolism Mutation Myoblasts/ metabolism Myositis, Inclusion Body/ enzymology/ genetics N-Acetylneuraminic Acid/ metabolism


      Professor Hanns Lochmuller
      Professor of Experimental Myology