MATR3基因新发点突变致散发性肌萎缩侧索硬化患者临床分析并文献复习  

Clinical analysis and literature review of sporadic amyotrophic lateral sclerosis caused by a novel mutation of MATR3 gene

作　　者：李杨 石强[1] 孙爽[2] Li Yang;Shi Qiang;Sun Shuang(Department of Neurology,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Department of Respriatory Medicine,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心神经内科医学部,北京100853 [2]解放军总医院第一医学中心呼吸内科,北京100853

出　　处：《中华神经科杂志》2022年第4期341-348,共8页Chinese Journal of Neurology

基　　金：国家自然科学基金面上项目(81771358)。

摘　　要：目的:对MATR3基因新发点突变致散发性肌萎缩侧索硬化(sALS)患者临床资料及相关文献进行分析。方法:收集2021年4月就诊于解放军总医院第一医学中心神经内科MATR3基因突变的1例sALS患者的临床资料,并对其行生化、肌电图、头颅磁共振成像(MRI)及基因检测。应用全外显子测序对先证者进行致病基因筛查,并应用Sanger测序技术对其进行突变位点的验证,通过SIFT Pred、Polyphen-2 HVAR Pred、MutationTaster Pred软件进行基因有害性预测。通过数据库检索,总结MATR3基因不同突变位点致ALS的临床特点。结果:先证者为69岁女性,以球肌力弱起病,逐渐累及颞肌、咬肌等颜面肌和四肢肌,体检除有上、下运动神经元受累外,还存在明显的颜面部肌肉萎缩。患者无ALS家族史。血清肌酸激酶、风湿免疫、肿瘤标志物等均正常,头颅MRI未见结构性病变和锥体束走行处异常信号,肌电图提示广泛神经源性损害、重复刺激波幅递减、瞬目反射和皮肤交感反应测定结果异常。基因筛查发现患者MATR3基因存在杂合突变c.1472A>G(p.Y491C),为错义突变,经软件预测为有害突变。结论:MATR3基因c.1472A>G(p.Y491C)位点变异可能为该患者的致病性突变,其临床表现除与经典ALS表现相似外还存在颜面部肌肉受累,肌电图提示皮肤交感反应和瞬目反射异常。Objective To analyze the clinical data and related literature of sporadic amyotrophic lateral sclerosis(sALS)caused by a new mutation of MATR3 gene.Methods A sALS patient with MATR3 gene mutation who was admitted to the Department of Neurology,the First Medical Center of Chinese People′s Liberation Army General Hospital was collected.The examination of biochemistry,electromyography,cranial magnetic resonance imaging(MRI)and genetic tests,etc,were performed.Whole exon sequencing was performed to screen the disease-causing genes.Sanger sequencing was also performed to validate the mutation sites of the patient.Genetic harmfulness was predicted by multiple computational softwares,including SIFT Pred,Polyphen-2 HVAR Pred and MutationTaster Pred.Clinical characteristics of ALS induced by different MATR3 gene mutation sites were summarized by database retrieval.Results The patient was a 69-year-old female,who began to show bulbar muscle weakness and then gradually developed to the facial muscles,including temporalis and masseter,and four limbs.In addition to the upper and lower motor neuron damage found in physical examination of the patient,the obvious facial muscle atrophy was also found in the patient.There was no family history of ALS in this patient.In terms of auxiliary examination,creatine kinase,rheumatism immunity and tumor markers were all normal.Cranial MRI showed no structural lesions and abnormal signals at the course of pyramidal tract.Electromyography suggested extensive neurogenic damage,decreased amplitude of repeated stimulation,abnormal measurement of blink reflex(BR)and skin sympathetic response(SSR).A heterozygous variant c.1472A>G(p.Y491C)of the MATR3 gene,which is a missense mutation,was detected in the patient.The variant was predicted as a harmful mutation by multiple computational softwares.Conclusions A variant c.1472A>G(p.Y491C)of the MATR3 gene may be the pathogenic mutation of the patient.The patient not only has similar clinical manifestations to those of classic ALS,but also has facial

关 键 词：肌萎缩侧索硬化 肌电描记术 MATR3基因 

分 类 号：R744.8[医药卫生—神经病学与精神病学]