中国CSF1R基因相关性白质脑病的临床及遗传学特点  

The phenotypic and genetic spectrum of colony-stimulating factor 1 receptor gene-related leukoencephalopathy in China

作　　者：邬静莹 张在强 柳青[3] 徐俊 徐蔚海[3] 武力勇[5] 吴志英[6] 王康[7] 邬剑军 邹漳钰[9] 蒋海山[10] 张巍[11] 葛巍 张玉虎[13] 张同霞[14] 张立霞[15] 王展航 凌丽[17] 周畅[18] 李云[19] 唐北沙[20] 汤建光[21] 钟平[22] 商靓 孙一忞 赵桂宪 赵秀鹤[14] 李宏福 胡炯[23] 姜杰玲 张超[22] 栾兴华 赵玉武[1] 田沃土 詹飞霞 钱晓杭 汤荟冬[24] 谭玉燕[24] 常春康[25] 赵佑山[25] 曹立 Wu Jingying;Zhang Zaiqiang;Liu Qing;Xu Jun;Xu Weihai;Wu Liyong;Wu Zhiying;Wang Kang;Wu Jianjun;Zou Zhangyu;Jiang Haishan;Zhang Wei;Ge Wei;Zhang Yuhu;Zhang Tongxia;Zhang Lixia;Wang Zhanhang;Ling Li;Zhou Chang;Li Yun;Tang Beisha;Tang Jianguang;Zhong Ping;Shang Liang;Sun Yimin;Zhao Guixian;Zhao Xiuhe;Li Hongfu;Hu Jiong;Jiang Jieling;Zhang Chao;Luan Xinghua;Zhao Yuwu;Tian Wotu;Zhan Feixia;Qian Xiaohang;Tang Huidong;Tan Yuyan;Chang Chunkang;Zhao Youshan;Cao Li(Department of Neurology,Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai 200233,China;China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Neurology,Peking Union Medical College Hospital,Beijing 100730,China;Center for Cognitive Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Neurology,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China;Department of Neurology,the First Affiliated Hospital,Zhejiang University,Hangzhou 310003,China;Department of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Neurology,Fujian Medical University Union Hospital,Fuzhou 350001,China;Department of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Department of Neurology,Peking University First Hospital,Beijing 100034,China;Department of Neurology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,China;Department of Neurology,Guangdong Provincial People's Hospital,Guangzhou 510080,China;Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Neurology,Weifang Hospital of Traditional Chinese Medicine,Weifang 261041,China;Department of Neurology,Guangdong 999 Brain Hospital,Guangzhou 510510,China;Department of Neurology,Affiliated Hospital of Hebei University,Baoding 071000,Chin

机构地区：[1]上海交通大学附属第六人民医院神经内科,200233 [2]首都医科大学附属北京天坛医院国家神经系统疾病临床医学研究中心,100070 [3]中国医学科学院北京协和医院神经科,100730 [4]首都医科大学附属天坛医院神经病学中心认知障碍科,北京100070 [5]首都医科大学宣武医院神经内科,北京100053 [6]浙江大学医学院附属第二医院神经内科,杭州310009 [7]浙江大学医学院附属第一医院神经内科,杭州310003 [8]复旦大学附属华山医院神经内科,上海200040 [9]福建医科大学附属协和医院神经内科,福州350001 [10]南方医科大学南方医院神经内科,广州510515 [11]北京大学第一医院神经内科,100034 [12]徐州医科大学附属医院神经内科,221002 [13]广东省人民医院神经内科,广州510080 [14]山东大学齐鲁医院神经内科,济南250012 [15]潍坊市中医院神经内科,261041 [16]广东三九脑科医院神经内科,广州510510 [17]河北大学附属医院神经内科,保定071000 [18]青岛大学附属医院神经内科,266003 [19]大理学院附属医院神经内科,671000 [20]中南大学湘雅医院神经内科,长沙410008 [21]中南大学湘雅二医院神经内科,长沙410011 [22]安徽医科大学附属宿州医院神经内科,234000 [23]上海交通大学医学院附属瑞金医院血液科,200025 [24]上海交通大学医学院附属瑞金医院神经内科,200025 [25]上海交通大学附属第六人民医院血液科,200233

出　　处：《中华神经科杂志》2021年第11期1109-1118,共10页Chinese Journal of Neurology

基　　金：国家自然科学基金(82071258,82071187,81870821)。

摘　　要：目的对中国CSF1R基因相关性白质脑病患者的临床资料进行总结及分析,以期明确中国患者的临床及遗传学特点。方法收集2018年4月1日至2021年1月31日在全国多中心共计22家医院神经内科确诊的CSF1R基因相关性白质脑病患者的临床及遗传相关病史资料,采用简易精神状态检查(MMSE)、蒙特利尔认知评估量表(MoCA)、磁共振严重性评分进行打分,并按性别分组,对不同性别的患者进行组间比较。结果共纳入患者62例,男∶女为1∶1.95,起病年龄(40.35±8.42)岁,主要症状是认知障碍(82.3%,51/62)及运动症状(77.4%,48/62)。全部患者的MMSE评分为(18.79±7.16)分,MoCA评分为(13.96±7.23)分。按性别分组后,男性的MMSE及MoCA评分分别为(22.06±5.31)、(18.08±5.60)分,显著高于女性[分别为(15.53±7.41)分,t=2.954,P=0.006;(10.15±6.26)分,t=3.328,P=0.003]。最常见的影像学特征为双侧非对称的白质改变(100.0%)。磁共振严重性评分为(27.42±11.40)分,其中女性白质病变评分[(22.94±8.39)分]显著高于男性[(17.62±8.74)分,t=-2.221,P<0.05]。62例患者中共发现36个CSF1R基因突变,其中c.2381T>C/p.I794T最为常见,17.9%(10/56)的先证者携带该位点。结论中国CSF1R基因相关性白质脑病患者在临床表现上以进行性运动和认知障碍为主,影像上以双侧非对称的白质改变为核心特征。该病在表型上存在性别差异,女性患者认知障碍及影像改变较男性更为严重。本研究共发现36个CSF1R基因突变,其中c.2381T>C/p.I794T为热点突变。Objective To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor(CSF1R)-related leukoencephalopathy,and clarify the phenotypic and genetic characteristics of Chinese patients.Methods Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1,2018 to January 31,2021 in the department of neurology of 22 hospitals in China was collected,and scores of Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment Scale(MoCA),magnetic resonance severity scale were evaluated.Group comparison was performed between male and female patients.Results A total of 62 patients were included,and the male-female ratio was 1∶1.95.The age of onset was(40.35±8.42)years.Cognitive impairment(82.3%,51/62)and motor symptoms(77.4%,48/62)were the most common symptoms.The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23,respectively,and the scores of two scales in male patients(22.06±5.31 and 18.08±5.60)were significantly higher than those in females(15.53±7.41,t=2.954,P=0.006;10.15±6.26,t=3.328,P=0.003).The most common radiographic feature was bilateral asymmetric white matter changes(100.0%),and the magnetic resonance imaging severity scale score was 27.42±11.40,while the white matter lesion score of females(22.94±8.39)was significantly higher than that of males(17.62±8.74,t=-2.221,P<0.05).A total of 36 CSF1R gene mutations were found in this study,among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9%(10/56)of the probands.Conclusions The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment,with bilateral asymmetrical white matter changes.In addition,there exist gender differences clinically,with severer cognitive impairment and imaging changes in female patients.Thirty-six CSF1R gene mutations were found in this study,and c.2381T>C/p.I794T was the hotspot mutation.

关 键 词：脑白质病 遗传性疾病 先天性 受体 集落刺激因子 突变 

分 类 号：R741[医药卫生—神经病学与精神病学]