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The glycomic sialylation profile of GNE Myopathy muscle cells does not point to consistent hyposialylation of individual glycoconjugates

      Highlights

      • GNE Myopathy patients culture cells were analysed for their glycomic sialylation profile.
      • Detailed glycomic analysis of glycoprotein and glycolipid derived glycans was undertaken.
      • No consistent differences were observed between healthy and GNE Myopathy patients' cells.
      • Consistent impaired sialylation of specific glycoconjugates was not detected in GNE myopathy.

      Abstract

      GNE Myopathy is a recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, and a typical muscle pathology. Although GNE, which is the mutated gene in the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the pathophysiological pathway leading from GNE mutations to the muscle phenotype in GNE Myopathy is still unclear. The obvious hypothesis of impaired sialylation in patients’ skeletal muscle as the cause of the disease is still controversial. In the present study we have investigated whether a distinctive altered pattern of sialylation in GNE Myopathy cultured muscle cells could be attributed to a specific glycoconjugate. Mass spectrometry based glycomic methodologies have been utilized to assess the sialylation level of protein N- and O-linked glycans and glycolipid derived glycans from patient and matched control samples. No consistent change in sialylation was detected in glycoconjugates. These results suggest potential additional roles for GNE that could account for the disease pathology.

      Keywords

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