Liu X, Duan X, Zhang Y, Sun A, Fan D
Department of Neurology, Peking University Third Hospital, Beijing, China.
Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China.
Eur J Neurol. 2020 Jul;27(7):1319-1326. doi: 10.1111/ene.14260. Epub 2020 May 12.
Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically heterogeneous group of disorders. The purpose of this study was to identify the genetic distribution of dHMNs in a large cohort of Chinese patients and provide insight into the underlying common pathophysiology of dHMNs.
Multi-gene panel testing or whole-exome sequencing was performed in 70 index patients with clinically diagnosed dHMN between January 2007 and December 2018. The clinical features, Charcot-Marie-Tooth (CMT) neuropathy scores and electrophysiological data at diagnosis were recorded.
Twenty-four causative mutations were identified in 70 index patients with dHMN (34.3%). Mutation in the HSPB1 gene was the most common cause of dHMN. Some CMT genes (MPZ, SH3TC2, GDAP1) were found to be related to dHMN with minor sensory involvement. Patients with a dHMN-plus phenotype (distal motor neuropathy and additional neurological deficits) carried variants in genes related to hereditary spastic paraplegia, amyotrophic lateral sclerosis and spinal muscular atrophy (FUS, KIF5A, KIF1B, ZFYVE26, DNAJB2).
Comprehensive genetic testing of dHMN patients allows for identification of the pathogenic mutation in one-third of cases. Pure motor neuropathies and motor neuropathies with minor sensory involvement share many genes with CMT disease. Causes for dHMN-plus phenotypes overlap with motor neuron disease.
远端遗传性运动神经病（dHMNs）是一组临床和遗传异质性疾病。本研究旨在确定中国一大群患者中dHMNs的基因分布，并深入了解dHMNs潜在的共同病理生理学机制。
对2007年1月至2018年12月期间70例临床诊断为dHMN的索引患者进行多基因panel检测或全外显子测序。记录诊断时的临床特征、夏科-马里-图斯（CMT）神经病评分和电生理数据。
在70例dHMN索引患者中鉴定出24个致病突变（34.3%）。HSPB1基因突变是dHMN最常见的病因。发现一些CMT基因（MPZ、SH3TC2、GDAP1）与伴有轻微感觉受累的dHMN有关。具有dHMN加表型（远端运动神经病和其他神经功能缺损）的患者携带与遗传性痉挛性截瘫、肌萎缩侧索硬化症和脊髓性肌萎缩症相关的基因变异（FUS、KIF5A、KIF1B、ZFYVE26、DNAJB2）。
对dHMN患者进行全面的基因检测可在三分之一的病例中鉴定出致病突变。纯运动神经病和伴有轻微感觉受累的运动神经病与CMT病有许多共同基因。dHMN加表型的病因与运动神经元病重叠。
