Article ; Online: 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.
Journal of the neurological sciences
2012 Volume 318, Issue 1-2, Page(s) 100–105
Abstract: Background: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, also ... disease onset. Participants with a homozygous mutation (p.V572L) in the N-acetylmannosamine kinase domain ... with mutations in the uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase and N-acetylmannosamine ...
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. |
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MeSH term(s) | Adolescent ; Adult ; Aged ; Carbohydrate Epimerases/genetics ; Carbohydrate Epimerases/metabolism ; Female ; Heterozygote ; Homozygote ; Humans ; Male ; Middle Aged ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Phenotype ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Protein Structure, Tertiary/genetics ; Severity of Illness Index ; Young Adult |
Chemical Substances | Multienzyme Complexes ; UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; N-acylmannosamine kinase (EC 2.7.1.60) ; Carbohydrate Epimerases (EC 5.1.3.-) ; UDP acetylglucosamine-2-epimerase (EC 5.1.3.14) |
Language | English |
Publishing date | 2012-07-15 |
Publishing country | Netherlands |
Document type | Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 80160-4 |
ISSN | 1878-5883 ; 0022-510X ; 0374-8642 |
ISSN (online) | 1878-5883 |
ISSN | 0022-510X ; 0374-8642 |
DOI | 10.1016/j.jns.2012.03.016 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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