Clinical characteristics and molecular genetic analysis of Korean patients with GNE myopathy

Yonsei Med J. 2013 May 1;54(3):578-82. doi: 10.3349/ymj.2013.54.3.578.

Abstract

Purpose: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy is an autosomal recessive neuromuscular disorder characterized by early adult-onset weakness of the distal muscles of the lower limbs. The clinical spectrum of GNE myopathy varies, and it is not clear how the same GNE gene mutations can result in different phenotypes. Here, we present clinical, pathological and genetic characteristics of twenty-one Korean patients with GNE myopathy.

Materials and methods: Twenty-one GNE myopathy patients were included in this study, conducted from 2004 to 2011. Based on medical records, patients' gender, onset age, family history, clinical history, serum creatine kinase (CK) level, neurologic examination, findings of muscle biopsy, muscle imaging findings and electrophysiologic features were extensively reviewed. Mutation of the GNE gene (9p13.3) was confirmed by DNA direct sequencing analysis in all patients.

Results: The mean onset age was 23.8±8.8 years (mean±SD). Patient serum CK levels were slightly to moderately elevated, ranging from 41 to 2610 IU. Among the patients, twelve patients were female and nine patients were male. Except for eight patients, all of the patients presented initially with only distal muscle weakness in the lower extremities. The most common mutation was V572L, followed by C13S.

Conclusion: The clinical manifestations of our patients with GNE mutations varied. Among twenty-one patients, thirteen patients showed the typical GNE myopathy phenotype. There was no relationship between clinical features and site of mutation. Therefore, we suggest that neither homozygous nor compound heterozygous models are correlated with disease phenotype or disease severity.

Keywords: GNE; genotype; phenotype.

MeSH terms

  • Adolescent
  • Adult
  • Creatine Kinase / blood
  • Distal Myopathies / diagnosis
  • Distal Myopathies / genetics*
  • Distal Myopathies / pathology
  • Female
  • Humans
  • Male
  • Multienzyme Complexes / genetics*
  • Republic of Korea
  • Sequence Analysis, DNA

Substances

  • Multienzyme Complexes
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
  • Creatine Kinase

Supplementary concepts

  • Distal myopathy, Nonaka type