...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuromuscular disorders: NMD >Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene
【24h】

Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene

机译：HSPB1基因突变引起的遗传性神经病的初步表型和自然史研究

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform the duration and outcome measures of any future trials. Clinical and neurophysiological data and lower limb muscle MRI were collected both prospectively and retrospectively from patients with mutations in HSPB1. The natural history was assessed by recording the weighted Charcot Marie Tooth Examination Score (CMTES) at annual intervals in a subset of patients. 20 patients from 14 families were recruited into the study. The average age of onset was in the 4th decade. Patients presented with a length dependent neuropathy but with early ankle plantar flexion weakness. Neurophysiology confirmed a motor neuropathy but also showed sensory nerve involvement in most patients. Cross sectional muscle MRI revealed soleus and medial gastrocnemius fat infiltration as an early signature of mutant HSPB1 disease. In this study neither semi quantitative muscle MRI, the CMTES nor neurophysiology were able to detect disease progression in HSPB1 neuropathy over 1 or 2 years. Further studies are therefore required to identify a suitable biomarker before clinical trials in HSPB1 neuropathy can be undertaken.
机译：HSPB1 突变是远端遗传性运动神经病变 （dHMN） 的最常见原因之一。该疾病的转基因小鼠模型已确定HDAC6抑制剂是治疗该病的有希望的治疗方法，为人体试验铺平了道路。因此，需要对 HSPB1 神经病变进行详细的表型和自然史研究，以便为任何未来试验的持续时间和结果测量提供信息。前瞻性和回顾性地收集了 HSPB1 突变患者的临床和神经生理学数据以及下肢肌肉 MRI。通过每年记录一部分患者的加权 Charcot Marie 牙齿检查评分 （CMTES） 来评估自然病程。来自 14 个家庭的 20 名患者被招募到研究中。平均发病年龄为第 4 个十年。患者表现为长度依赖性神经病变，但伴有早期踝关节跖屈无力。神经生理学证实了运动神经病变，但也显示大多数患者有感觉神经受累。横断面肌肉 MRI 显示比目鱼肌和腓肠肌内侧脂肪浸润是突变型 HSPB1 疾病的早期特征。在这项研究中，半定量肌肉 MRI、CMTES 和神经生理学都无法检测到 HSPB1 神经病变在 1 或 2 年内的疾病进展。因此，在进行 HSPB1 神经病变的临床试验之前，需要进一步的研究以确定合适的生物标志物。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号