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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.

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.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Mori-Yoshimura M,Monma K,Suzuki N,Aoki M,Kumamoto T,Tanaka K,Tomimitsu H,Nakano S,Sonoo M,Shimizu J,Sugie K,Nakamura H,Oya Y,Hayashi YK,Malicdan MC,Noguchi S,Murata M,Nishino I

doi

10.1016/j.jns.2012.03.016

subject

Has Abstract

pub_date

2012-07-15 00:00:00

pages

100-5

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(12)00157-8

journal_volume

318

pub_type

杂志文章

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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.