Novel GNE compound heterozygous mutations in a GNE myopathy patient

Muscle Nerve. 2013 Oct;48(4):594-8. doi: 10.1002/mus.23862. Epub 2013 Aug 30.


Introduction: Molecular studies have revealed that some patients with myopathies with rimmed vacuoles have pathogenic mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and Z-band alternatively spliced PDZ motif-containing protein (ZASP) genes.

Methods: We investigated a patient with distal myopathy with rimmed vacuoles by muscle biopsy and sequenced 6 candidate genes.

Results: The patient carried GNE compound heterozygous missense mutations (p.V421A and p.N635K) and a ZASP variant (p.D673N). This patient also presented with distal weakness sparing the quadriceps muscles and had atypical results for Z-band-associated protein immunostaining. This finding indicates that the GNE mutations are pathogenic, and the diagnosis is compatible with GNE myopathy.

Conclusions: By combining pathological studies and candidate gene screening, we identified a patient with GNE myopathy due to novel GNE compound heterozygous mutations.

Keywords: GNE myopathy; UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE); Z-band alternatively spliced PDZ motif-containing protein (ZASP); distal myopathy with rimmed vacuoles; myofibrillar myopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Female
  • Genetic Carrier Screening*
  • Humans
  • LIM Domain Proteins / genetics*
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / pathology*
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology
  • Mutation, Missense / genetics
  • Vacuoles / genetics
  • Vacuoles / pathology


  • Adaptor Proteins, Signal Transducing
  • LDB3 protein, human
  • LIM Domain Proteins
  • Multienzyme Complexes
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase