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Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy)

Title
Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy)
Authors
Cho, AnnaHayashi, Yukiko K.Monma, KazunariOya, YasushiNoguchi, SatoruNonaka, IkuyaNishino, Ichizo
Ewha Authors
조안나
SCOPUS Author ID
조안나scopus
Issue Date
2014
Journal Title
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
ISSN
0022-3050JCR Link

1468-330XJCR Link
Citation
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY vol. 85, no. 8, pp. 912 - 915
Publisher
BMJ PUBLISHING GROUP
Indexed
SCIE; SCOPUS WOS
Document Type
Article
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.
DOI
10.1136/jnnp-2013-305587
Appears in Collections:
의과대학 > 의학과 > Journal papers
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