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
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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DOI：
10.1016/j.jns.2012.03.016
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发表时间：
2012-07-15
影响因子：
4.4
通讯作者：
Nishino, Ichizo
中科院分区：
文献类型：
--
作者：
Mori-Yoshimura, Madoka;Monma, Kazunari;Nishino, Ichizo
背景：氨基葡萄糖(UDP-N-acetyl)-2-epimerase/N-acetylmannosamine激酶(GNOE)肌病，又称空泡远端肌病或遗传性包涵体肌病，是一种罕见的常染色体隐性遗传病，由GNE基因突变引起。方法：对GNE肌病患者进行问卷调查。结果：71例GNE肌病患者(男27例，女44例，平均年龄43.1+/-13.0(平均+/-SD)岁)完成了问卷调查。首发症状(例如，足下垂和下肢无力)出现的平均年龄为24.8±8.3岁。在71名参与者中，11名(15.5%)具有行走能力，发病后失去行走能力的中位时间为17.0+/-2.1年。与尿苷二磷酸-N-乙酰氨基葡萄糖(UDP-GlcNAc)2-差向异构酶和N-乙酰甘露糖激酶结构域突变的复合杂合子参与者(ED/KD参与者：26.3+/-7.3对21.2+/-11.1年)相比，具有N-乙酰甘露糖激酶域纯合子突变的参与者(KD/KD参与者：26.3+/-7.3岁对21.2+/-11.1年)的发病时间更早。在调查时，KD/KD参与者比ED/KD参与者更频繁地处于非活动状态(80%比50%)。数据通过17名门诊患者的病历进行了验证。结论：与杂合子ED/KD患者相比，纯合子KD/KD患者表现出更严重的表型。(C)2012爱思唯尔B.V.保留所有权利。
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. (C) 2012 Elsevier B.V. All rights reserved.