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

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• 作者：Madoka Mori-Yoshimura^a ; ^{yoshimur@ncnp.go.jp} ; Kazunari Monma^b ; Naoki Suzuki^c ; Masashi Aoki^c ; Toshihide Kumamoto^d ; Keiko Tanaka^e ; Hiroyuki Tomimitsu^f ; Satoshi Nakano^g ; Masahiro Sonoo^h ; Jun Shimizuⁱ ; Kazuma Sugie^j ; Harumasa Nakamura^a ; ^k ; Yasushi Oya^a ; Yukiko K. Hayashi^b ; May Christine V. Malicdan^b ; Satoru Noguchi^b ; Miho Murata^a ; Ichizo Nishino^b
• 关键词：GNE myopathy ; Distal myopathy with rimmed vacuoles ; Hereditary inclusion body myopathy ; Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase ; (UDP-N-acetyl)-2-epimerase domain ; N-acetylmannosamine kinase domain ; Questionnaire ; Natural history
• 刊名：Journal of the Neurological Sciences
• 出版年：2012
• 期刊代码：178_0022510x
• 类别：med
• 出版时间：15 July, 2012
• 卷：318
• 期：1-2
• 页码：100-105
• 文件大小：254 K

摘要

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 卤 13.0 (mean 卤 SD) years) completed the questionnaire. Initial symptoms (e.g., foot drop and lower limb weakness) appeared at a mean age of 24.8 卤 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 卤 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 卤 7.3 vs. 21.2 卤 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.