bims-meglyc Biomed News
on Metabolic disorders affecting glycosylation
Issue of 2024‒06‒16
three papers selected by
Silvia Radenkovic, UMC Utrecht



  1. J AAPOS. 2024 Jun 12. pii: S1091-8531(24)00234-9. [Epub ahead of print] 103954
      Congenital disorders of glycosylation type I (CDG-I) are a group of autosomal recessive genetic multisystem disorders that arise from defective glycoprotein biosynthesis. Although ocular abnormalities have been described in patients with CDG-I, few ocular abnormalities have been associated with ALG12-CDG (CDG-Ig), a rare subtype of CDG-I. We report a case of Duane syndrome, a congenital strabismus syndrome, in a 17-year-old young woman with ALG12-CDG.
    DOI:  https://doi.org/10.1016/j.jaapos.2024.103954
  2. J Neuromuscul Dis. 2024 Jun 12.
      Background: GNE Myopathy is a unique recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, caused by mutations in the GNE gene which is a key enzyme in the biosynthesis of sialic acid. To date, the precise pathophysiology of the disease is not well understood and no reliable animal model is available. Gne KO is embryonically lethal in mice.Objective: To gain insights into GNE function in muscle, we have generated an inducible muscle Gne KO mouse. To minimize the contribution of the liver to the availability of sialic acid to muscle via the serum, we have also induced combined Gne KO in liver and muscle.
    Methods: A mouse carrying loxp sequences flanking Gne exon3 was generated by Crispr/Cas9 and bred with a human skeletal actin (HAS) promoter driven CreERT mouse. Gne muscle knock out was induced by tamoxifen injection of the resulting homozygote GneloxpEx3loxp/HAS Cre mouse. Liver Gne KO was induced by systemic injection of AAV8 vectors carrying the Cre gene driven by the hepatic specific promoter of the thyroxine binding globulin gene.
    Results: Characterization of these mice for a 12 months period showed no significant changes in their general behaviour, motor performance, muscle mass and structure in spite of a dramatic reduction in sialic acid content in both muscle and liver.
    Conclusions: We conclude that post weaning lack of Gne and sialic acid in muscle and liver have no pathologic effect in adult mice. These findings could reflect a strong interspecies versatility, but also raise questions about the loss of function hypothesis in Gne Myopathy. If these findings apply to humans they have a major impact on therapeutic strategies.
    Keywords:  GNE; GNE KO model; GNE myopathy; animal model; liver GneKO; muscle GneKO; sialic acid
    DOI:  https://doi.org/10.3233/JND-240056