青少年型重症肌无力的临床特征和相关基因变异情况分析  

Analysis of clinical characteristics and related genetic variation of juvenile myasthenia gravis

作　　者：杨文昊 鲁亚茹 邱力[1] 欧昶毅[1] 林中强[1] 黄志东[1] 刘卫彬[1] Yang Wenhao;Lu Yaru;Qiu Li;Ou Changyi;Lin Zhongqiang;Huang Zhidong;Liu Weibin(Department of Neurology,the First Affiliated Hospital,Sun Yat-sen University Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases,National Key Clinical Department and Key Discipline of Neurology,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院神经科,广东省重大神经疾病诊治研究重点实验室,国家临床重点专科和国家重点学科,广州510080

出　　处：《中华医学杂志》2022年第19期1445-1449,共5页National Medical Journal of China

基　　金：国家自然科学基金(81620108010, 81873772);中山大学临床研究5010计划项目(2010003);华南神经疾病早期干预及功能修复研究国际合作基地(2015B050501003)。

摘　　要：目的分析青少年型重症肌无力(MG)患者的临床特征及相关基因变异特点。方法收集2019年6月至2020年5月在中山大学附属第一医院神经内科就诊的青少年型MG患者的临床资料, 征得患者知情同意后留取血标本, 应用Illumina平台对血标本进行全外显子检测, 运用生物信息软件及SPSS 22.0进行数据处理及结果分析。结果根据纳入和排除标准共纳入54例青少年型MG患者, 男28例, 女26例, 起病年龄(3.79±0.89)岁。入组患者中眼肌型患者52例(96.3%), 54例患者的MG-ADL评分为(3.44±0.44)分, AChR-Ab抗体滴度为(5.88±2.45)nmol/L。2例患者合并胸腺增生, 5例患者有MG家族史。在54例患者中共发现了169个变异基因, 其中肌联蛋白titin(TTN)基因变异例数最多, 共发生变异17例(31.5%)。TTN基因变异组中, 有7例(7/17)患者有眼球固定表现, 非变异组中有4例(10.8%)患者出现眼球固定症状, 两组比较差异有统计学意义(P=0.016)。突触核包膜蛋白1(SYNE1)和兰尼碱受体1(RYR1)基因变异共7例(13.2%), 未发现此类基因变异与MG临床表现的明确关系。结论青少年型MG的好发人群为学龄前儿童, 无性别差异, 以眼肌型多见。青少年型MG中TTN基因变异比例较高, 提示该基因可能是青少年型MG患者的潜在治疗靶点。Objective To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis(MG)patients.Methods We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020.After obtaining the patient′s informed consent,the blood samples were collected.The Whole Exome Sequencing(WES)was performed on peripheral blood samples.And use biological information software and SPSS 22.0 for data processing and result analysis.Results According to the inclusion and exclusion criteria,54 patients with juvenile MG were included,28 males and 26 females.And the average age of onset was(3.79±0.89)years.Among the enrolled patients,there were 52(96.3%)patients with ocular MG,the MG-ADL scores of 54 patients were(3.44±0.44)points,and the titer of AChR antibody was(5.88±2.45)nmol/L.Two patients had thymic hyperplasia,and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients,of which TTN gene variants had the largest number,with a total of 17 variants(31.5%).In the TTN gene variant group,7(41.2%)patients had eye fixation symptoms,and 4(10.8%)patients in the non-mutation group had eye fixation symptoms.And The difference between the two groups was statistically significant(P=0.016).In addition,the synaptic nucleus envelope protein-1(SYNE1)and the ryanodine receptor-1(RYR1)gene variations were also found in 7 cases(13.2%),and no clear relationship between these gene variations and clinical manifestations of MG was found.Conclusions The incidence of juvenile MG was preschoolers with no gender difference,and ocular MG was more common.The proportion of TTN gene variation in adolescent MG was higher,suggesting that this gene may be a potential therapeutic target for juvenile MG patients.

关 键 词：重症肌无力 青少年 全外显子测序 横断面研究 

分 类 号：R746.1[医药卫生—神经病学与精神病学]