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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.

AbstractBACKGROUND:
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.
AuthorsMadoka 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
JournalJournal of the neurological sciences (J Neurol Sci) Vol. 318 Issue 1-2 Pg. 100-5 (Jul 15 2012) ISSN: 1878-5883 [Electronic] Netherlands
PMID22507750 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Multienzyme Complexes
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
  • Phosphotransferases (Alcohol Group Acceptor)
  • N-acylmannosamine kinase
  • Carbohydrate Epimerases
  • UDP acetylglucosamine-2-epimerase
Topics
  • Adolescent
  • Adult
  • Aged
  • Carbohydrate Epimerases (genetics, metabolism)
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes (genetics, metabolism)
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
  • Protein Structure, Tertiary (genetics)
  • Severity of Illness Index
  • Young Adult

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