Abstract:

Objective: To summarize the clinical manifestations and genetic characteristics of patients with Charcot-Marie-Tooth disease (CMT) caused by ARSs gene variation. Methods and Results: A total of 12 probands with clinical diagnosis of CMT were selected from The First Affiliated Hospital of Fujian Medical University from January 1997 to February 2024 and included in the clinical registration cohort of the hospital. Clinical symptoms: 10 patients had normal proximal limb muscle strength, while the distal limb muscle strength was seriously involved. Most muscular atrophy occurred below ankle joint and wrist joint. Two patients had subjective numbness of limbs, and one patient had reduced symmetry sensation on superficial sensory examination. Tendon reflexes were normal in only one patient. EMG characteristics: for the 11 probands, the median nerve motor nerve conduction velocity (MNCV) ranged from 0 to 65.70 m/s, with an average of 36.67 m/s, and the median nerve compound muscle action potential (CMAP) ranged from 0 to 19.50 mV, with an average of 5.42 mV. ARSs gene variation analysis: there were 4 ARSs gene variants, including GARS1, YARS1, AARS1 and SARS1. Among the 8 GARS1 gene mutation sites (c.1235G > A, c.598G > C, c.362G > A, c.1415A > G, c.637C > T, c.374A > G, c.722G > T, c.1000A > T), c. 598G > C and c. 722G > T had not been reported at home and abroad. EMG showed 5 probands were intermediate CMT (ICMT) and 3 were CMT₂. Among the 2 YARS1 gene mutation sites (c. 1333A > G, c. 787T > C), C. 787T > C has not been reported at home and abroad, and the 2 probands were CMT1 and ICMT. One proband with AARS1 gene mutation (c.896C > T), the EMG showed CMT₂; and there was one proband with SARS1 gene mutation (c.1187C > T), and the EMG showed ICMT. Conclusions: CMT caused by ARSs gene variation mainly causes hereditary motor neuropathy with or without sensory involvement, and the main clinical phenotypes are CMT₂ and ICMT. Different ARSs gene variation-related CMT patients have different clinical manifestations, and gene detection should be performed to confirm the diagnosis. The genetic spectrum of CMT was expanded to provide a basis for disease diagnosis and genetic counseling.

Key words: Charcot-Marie-Tooth disease, Amino acyl-tRNA synthetases, Genes, Mutation, Phenotype, Pedigree

摘要：

目的: 总结ARSs基因变异致腓骨肌萎缩症（CMT）的临床表现和遗传学特征。方法与结果: 选择1997年1月至2024年2月福建医科大学附属第一医院临床注册登记队列中临床拟诊腓骨肌萎缩症的12个家系共12例先证者。临床症状，10例四肢近端肌力正常，远端受累严重；肌萎缩多出现于踝关节及腕关节以下；2例主观肢体麻木感，1例对称性浅感觉减退；仅1例腱反射正常。电生理学特点，11例正中神经运动神经传导速度平均为36.67 m/s，正中神经复合肌肉动作电位平均为5.42 mV。ARSs基因变异分析，包括GARS1、YARS1、AARS1和SARS1共4种ARSs基因变异，8个GARS1基因突变位点（c.1235G > A、c.598G > C、c.362G > A、c.1415A > G、c.637C > T、c.374A > G、c.722G > T、c.1000A > T）中c.598G > C、c.722G > T国内外尚未见诸报道；肌电图提示5例先证者为中间型（ICMT型），3例为轴索型（CMT₂型）。2个YARS1基因突变位点c.1333A > G、c.787T > C中c.787T > C国内外尚未见诸报道；2例先证者分别为脱髓鞘型（CMT1型）和ICMT型；AARS1基因c.896C > T突变1例，为CMT₂型；SARS1基因c.1187C > T突变1例，为ICMT型。结论: ARSs基因变异致腓骨肌萎缩症主要引起伴或不伴感觉受累的遗传性运动神经病，主要临床分型为CMT₂型及ICMT型，不同ARSs基因变异致腓骨肌萎缩症患者存在不同临床表现，应进行基因检测以明确诊断。本研究扩大了腓骨肌萎缩症的遗传谱，为疾病诊断和遗传咨询提供了依据。

关键词: 夏科-马里-图斯病, 氨酰基tRNA合成酶类, 基因, 突变, 表型, 系谱