3例腓骨肌萎缩症患者临床特征和基因突变分析  

Clinical characteristics and genetic mutation of Charcot-Marie-Tooth disease in three patients

作　　者：李晓溪[1] 金佳丽[2] 刘卓[2] 王翀[2] 徐运[2] 张梅娟[2] LI Xiaoxi;JIN Jiali;LIU Zhuo;WANG Chong;XU Yun;ZHANG Meijuan(Department of Emergency,Nanjing Drum Tower Hospital,Medical School of Nanjing University,Nanjing,Jiangsu 210008,China;Department of Neurology,Nanjing Drum Tower Hospital,Medical School of Nanjing University,Nanjing,Jiangsu 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院急诊科,江苏南京210008 [2]南京大学医学院附属鼓楼医院神经内科,江苏南京210008

出　　处：《中华实用诊断与治疗杂志》2023年第7期701-705,共5页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金面上项目(81571135,81971112);江苏省自然科学基金面上项目(BK20191116)。

摘　　要：目的 总结腓骨肌萎缩症的临床表现、实验室检查和遗传学特征。方法 回顾性分析2020年1月—2022年12月南京鼓楼医院诊治的3例腓骨肌萎缩症患者的临床特征和基因检测结果。结果 3例均隐匿性起病,临床主要表现为肌肉萎缩、下肢无力、行走不稳,伴有高弓足、足下垂、双足难以背屈,逐渐缓慢加重;肌电图检查显示四肢神经源性损害,下肢受累更重;神经内科查体显示四肢远端肌力下降。例1、例3患者行神经节苷脂抗体谱检测,未见异常。3例脑脊液常规及细菌学检查均正常,蛋白及白蛋白水平增高,例1脑脊液压力增高。MRI检查显示例2患者臂丛神经增粗,例2、例3双下肢肌肉脂肪浸润,例3患者双侧胫腓骨周围肌组织弥漫性渗出改变。例1患者chr17:14050864-15175466区域(包含PMP22基因外显子区)存在大片段重复突变,导致腓骨肌萎缩症1A型;例2患者PMP22基因存在大片段重复突变,符合腓骨肌萎缩症1A型基因突变特征;例3患者PMP22基因未见明显异常,存在GJB1基因c.367C>T (p.His123Tyr)和c.491G>T (p.Arg164Leu)错义突变,致病性分析结果显示c.491G>T位点为疑似致病突变,可导致腓骨肌萎缩症X1型。结论 腓骨肌萎缩症临床主要表现为进行性加重的四肢肌肉萎缩、远端肌力下降,基因检测有助于早期明确诊断。Objective To analyze the clinical manifestation,laboratory results and genetic characteristics of Charcot-Marie-Tooth(CMT) disease.Methods The clinical characteristics and genetic testing results of three patients with CMT disease diagnosed and treated in Nanjing Drum Tower Hospital from January 2020 to December 2022 were retrospectively analyzed.Results Three patients had occult onset,followed by gradual worsening of their conditions which were mainly manifested as muscle atrophy,lower extrimity weakness,and unstable walking accompanied by high arched feet,drop feet and difficult dorsiflexion of both feet.Electromyography showed neurogenic lesions in the extremities,with more severe involvement in the lower extremities.Neurological examination showed a decreased muscle strength in the distal extremities.Ganglioside antibody spectrum was detected in patient 1 and 3,and no abnormality was found.Cerebrospinal fluid routine and bacteriological examination were normal in 3 patients,and protein and albumin levels increased.Cerebrospinal fluid pressure increased in patient 1.MRI examination showed brachial plexus thickening in patient 2,muscle fat infiltration in both lower extremities in patient 2 and 3,and diffuse exudation of muscle tissue in bilateral tibiofibula in patient 3.The gene detection results demonstrated a large fragment duplication mutation in chr17:14050864-15175466(including PMP22 exon),which resulted in CMT1A in patient 1.A large fragment duplication mutation in PMP22 gene was found in patient 2,which confirmed to the gene mutation features of CMT1A.Patient 3 was found c.367c>t(p.His123Tyr) and c.491g>t(p.Arg164Leu) missense mutations of GJB1 gene but no abnormality in PMP22 gene;the pathogenic analysis showed c.491G>T site was suspected to be pathogenic mutation,which was associated with CMTX1.Conclusion CMT disease is clinically manifested with extremities muscle atrophy and decreased muscle strength in the distal extremities,and the genetic testing contributes to the early diagnosis.

关 键 词：腓骨肌萎缩症 四肢肌肉萎缩 肌力下降 PMP22基因 GJB1基因 

分 类 号：R746.4[医药卫生—神经病学与精神病学]