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Research paper
Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy)
  1. Anna Cho1,
  2. Yukiko K Hayashi1,2,3,
  3. Kazunari Monma1,
  4. Yasushi Oya4,
  5. Satoru Noguchi1,
  6. Ikuya Nonaka1,
  7. Ichizo Nishino1,2
  1. 1Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
  2. 2Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
  3. 3Department of Neurophysiology, Tokyo Medical University, Tokyo, Japan
  4. 4Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
  1. Correspondence to Professor Yukiko K Hayashi, Department of Neurophysiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku, Tokyo 160-8402, Japan; yhayashi{at}tokyo-med.ac.jp

Abstract

Background GNE myopathy (also called distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy) is an autosomal recessive myopathy characterised by skeletal muscle atrophy and weakness that preferentially involve the distal muscles. It is caused by mutations in the gene encoding a key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).

Methods We analysed the GNE gene in 212 Japanese GNE myopathy patients. A retrospective medical record review was carried out to explore genotype–phenotype correlation.

Results Sixty-three different mutations including 25 novel mutations were identified: 50 missense mutations, 2 nonsense mutations, 1 insertion, 4 deletions, 5 intronic mutations and 1 single exon deletion. The most frequent mutation in the Japanese population is c.1714G>C (p.Val572Leu), which accounts for 48.3% of total alleles. Homozygosity for this mutation results in more severe phenotypes with earlier onset and faster progression of the disease. In contrast, the second most common mutation, c.527A>T (p.Asp176Val), seems to be a mild mutation as the onset of the disease is much later in the compound heterozygotes with this mutation and c.1714G>C than the patients homozygous for c.1714G>C. Although the allele frequency is 22.4%, there are only three homozygotes for c.527A>T, raising a possibility that a significant number of c.527A>T homozygotes may not develop an apparent disease.

Conclusions Here, we report the mutation profile of the GNE gene in 212 Japanese GNE myopathy patients, which is the largest single-ethnic cohort for this ultra-orphan disease. We confirmed the clinical difference between mutation groups. However, we should note that the statistical summary cannot predict clinical course of every patient.

  • Genetics
  • Muscle Disease
  • Myopathy

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