Chao Hua-Chuan, Hsiao Cheng-Tsung, Lai Kuan-Lin, Tsai Yu-Shuen, Lin Kon-Ping, Liao Yi-Chu, Lee Yi-Chung
Department of Neurology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Neurology, Department of Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taiwan.
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
J Formos Med Assoc. 2023 Feb;122(2):132-138. doi: 10.1016/j.jfma.2022.08.008. Epub 2022 Aug 26.
Mutations in the neurofilament light polypeptide gene (NEFL) are an uncommon cause of Charcot-Marie-Tooth disease (CMT). The aim of this study is to elucidate the clinical characteristics and genetic spectrum of NEFL-related neuropathy in a Taiwanese CMT cohort.
Mutational analysis of the coding regions of NEFL was performed by Sanger sequencing or targeted resequencing. Twenty-one patients from nine CMT pedigrees, identified from a cohort of 508 unrelated CMT patients, were found to have a NEFL mutation. Genetic, clinical and electrophysiological features were analyzed.
Six NEFL mutations were identified, including two novel ones (p.P8S, p.N98Y). NEFL p.E396K was the most common mutation, accounting for 33.3% of the patients in our cohort. All patients manifested sensorimotor polyneuropathy with a mean age of disease onset of 13.5 ± 9.6 (1-40) years. Their motor nerve conduction velocities (MNCVs) of the ulnar nerve ranged from 22.1 to 48.7 m/s. Seventy percent of the patients could be classified as intermediate CMT with ulnar MNCVs between 25 and 45 m/s. Six of the 21 patients (28.6%) had additional features of central nervous system (CNS) involvement, including motor developmental delay, spasticity, cerebellar signs, neuropathic pain and scoliosis.
NEFL mutations account for 1.8% (9/508) of the CMT patients in Taiwan. The present study delineates the clinical and genetic characteristics of NEFL-related neuropathy in Taiwan, and highlights that ulnar MNCV above 25 m/s and CNS involvement may serve as diagnostic clues for NEFL-related neuropathy.
神经丝轻链多肽基因（NEFL）突变是夏科-马里-图斯病（CMT）的一种罕见病因。本研究旨在阐明台湾CMT队列中NEFL相关神经病变的临床特征和基因谱。
通过桑格测序或靶向重测序对NEFL编码区进行突变分析。从508例无亲缘关系的CMT患者队列中鉴定出9个CMT家系的21例患者存在NEFL突变。对其遗传、临床和电生理特征进行分析。
鉴定出6种NEFL突变，包括2种新突变（p.P8S、p.N98Y）。NEFL p.E396K是最常见的突变，占我们队列中患者的33.3%。所有患者均表现为感觉运动性多发性神经病变，疾病平均发病年龄为13.5±9.6（1 - 40）岁。尺神经运动神经传导速度（MNCV）范围为22.1至48.7 m/s。70%的患者可归类为中度CMT，尺神经MNCV在25至45 m/s之间。21例患者中有6例（28.6%）具有中枢神经系统（CNS）受累的其他特征，包括运动发育迟缓、痉挛、小脑体征、神经性疼痛和脊柱侧弯。
NEFL突变占台湾CMT患者的1.8%（9/508）。本研究描述了台湾NEFL相关神经病变的临床和遗传特征，并强调尺神经MNCV高于25 m/s和CNS受累可能作为NEFL相关神经病变的诊断线索。
