Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations

Madoka Mori-Yoshimura, Kazunari Monma, Naoki Suzuki, Masashi Aoki, Toshihide Kumamoto, Keiko Tanaka, Hiroyuki Tomimitsu, Satoshi Nakano, Masahiro Sonoo, Jun Shimizu, Kazuma Sugie, Harumasa Nakamura, Yasushi Oya, Yukiko K. Hayashi, May Christine V. Malicdan, Satoru Noguchi, Miho Murata, Ichizo Nishino

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Background: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, also called distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy (HIBM), is a rare, progressive autosomal recessive disorder caused by mutations in the GNE gene. Here, we examined the relationship between genotype and clinical phenotype in participants with GNE myopathy. Methods: Participants with GNE myopathy were asked to complete a questionnaire regarding medical history and current symptoms. Results: A total of 71 participants with genetically confirmed GNE myopathy (27 males and 44 females; mean age, 43.1 ± 13.0 (mean ± SD) years) completed the questionnaire. Initial symptoms (e.g., foot drop and lower limb weakness) appeared at a mean age of 24.8 ± 8.3 years. Among the 71 participants, 11 (15.5%) had the ability to walk, with a median time to loss of ambulation of 17.0 ± 2.1 years after disease onset. Participants with a homozygous mutation (p.V572L) in the N-acetylmannosamine kinase domain (KD/KD participants) had an earlier disease onset compared to compound heterozygous participants with mutations in the uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase and N-acetylmannosamine kinase domains (ED/KD participants; 26.3 ± 7.3 vs. 21.2 ± 11.1 years, respectively). KD/KD participants were more frequently non-ambulatory compared to ED/KD participants at the time of survey (80% vs. 50%). Data were verified using medical records available from 17 outpatient participants. Conclusions: Homozygous KD/KD participants exhibited a more severe phenotype compared to heterozygous ED/KD participants.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalJournal of the neurological sciences
Volume318
Issue number1-2
DOIs
Publication statusPublished - 2012 Jul 15

Keywords

  • (UDP-N-acetyl)-2-epimerase domain
  • Distal myopathy with rimmed vacuoles
  • GNE myopathy
  • Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase
  • Hereditary inclusion body myopathy
  • N-acetylmannosamine kinase domain
  • Natural history
  • Questionnaire

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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