<em>LRRK2</em>基因突变相关语义变异型原发性进行性失语一例并文献复习

doi:10.3969/j.issn.1672-6731.2020.06.012

中国现代神经疾病杂志 ›› 2020, Vol. 20 ›› Issue (6): 541-545. doi: 10.3969/j.issn.1672-6731.2020.06.012

2 LRRK2基因突变相关语义变异型原发性进行性失语一例并文献复习

郭仕鹏¹, 陈达宁², 雷晓阳¹, 张安妮¹, 吴旭玲¹, 李娅¹, 贺电¹

1. 550004 贵阳, 贵州医科大学附属医院神经内科;
2. 550004 贵阳, 贵州省第二人民医院心身科

收稿日期:2020-06-02 出版日期:2020-06-25 发布日期:2020-06-24
通讯作者: 贺电,Email:hedian@gmc.edu.cn
基金资助:
贵州省科技计划项目（项目编号：［2018］4615-2）

LRRK2 gene mutation-associated semantic variant primary progressive aphasia: one case report and literatures review

GUO Shi-peng¹, CHEN Da-ning², LEI Xiao-yang¹, ZHANG An-ni¹, WU Xu-ling¹, LI Ya¹, HE Dian¹

1 Department of Neurology, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China;
2 Department of Psychosomatic Medicine, Guizhou Second Provincial People's Hospital, Guiyang 550004, Guizhou, China

Received:2020-06-02 Online:2020-06-25 Published:2020-06-24
Supported by:
This study was supported by Science and Technology Plan Program in Guizhou Province, China (No. [2018] 4615-2).

摘要/Abstract

摘要：

目的报告1例LRRK2基因突变相关语义变异型原发性进行性失语患者的临床表型和基因突变特点。方法与结果 对1例以语言理解障碍为首发症状患者的临床表现、神经心理学变化及语言功能障碍特点、脑脊液生物学标志物和头部影像学变化，以及基因检测结果进行分析，并结合相关文献进行病因讨论。结果显示，其主要表现为单词理解困难和找词困难；汉语失语成套测验提示以颞叶功能损害为主。头部MRI检查双侧额叶及颞叶呈不对称萎缩，以左侧更为显著；¹⁸F-FDG PET呈现双侧颞叶前部及双侧额叶葡萄糖代谢降低现象。认知功能障碍和运动障碍基因检测表明存在LRRK2基因外显子25 3468G > C杂合突变，目前尚未被所有基因数据库所收录，临床诊断为语义变异型原发性进行性失语。结论 LRRK2基因突变很可能是由于其编码的LRRK2蛋白结构和功能改变，引起tau蛋白病理改变，进而导致额颞叶变性萎缩和语义变异型原发性进行性失语。该基因突变的发现扩大了额颞叶变性的基因突变谱。

关键词: 失语, 原发进行性, 额颞叶痴呆, 基因, 突变

Abstract:

Objective To report the clinical phenotype and gene mutation characteristics of a case with leucine-rich repeat kinase 2 (LRRK2) gene mutation-associated semantic variant primary progressive aphasia. Methods and Results The clinical data of a patient with language comprehension impairment as the first symptom were analyzed, including clinical manifestations, neuropsychological and linguistic assessments, cerebrospinal fluid biomarker tests, brain images and genetic testings. We made a systematic discussion in combination with relevant literatures. The results showed that the main clinical manifestations of the patient were difficulty in understanding words and difficulty in finding words. Aphasia Battery of Chinese test showed that the temporal lobe damage was prominent. Head MRI showed asymmetric atrophy of the bilateral frontal and temporal lobes, which was significant on the left side. ¹⁸F-FDG PET further suggested that the glucose metabolism in the bilateral anterior temporal lobes and bilateral frontal lobes was reduced. Cognitive impairment and dyskinesia gene detection revealed that the patient had a heterozygous mutation in exon 25 3468G > C of LRRK2 gene, which was the first report at home and abroad. The clinical diagnosis was semantic variant primary progressive aphasia. Conclusions This patient carries mutations in the LRRK2 gene. It is likely that due to changes in the structure and function of the encoded LRRK2 protein, which causes tau pathologic changes, and in turn leads to the degeneration and atrophy of the frontotemporal lobe and semantic variant primary progressive aphasia. The discovery of this gene mutation expands the gene mutation spectrum of frontotemporal lobe dege-neration.

Key words: Aphasia,primary progressive, Frontotemporal dementia, Genes, Mutation

郭仕鹏, 陈达宁, 雷晓阳, 张安妮, 吴旭玲, 李娅, 贺电. LRRK2基因突变相关语义变异型原发性进行性失语一例并文献复习[J]. 中国现代神经疾病杂志, 2020, 20(6): 541-545.

GUO Shi-peng, CHEN Da-ning, LEI Xiao-yang, ZHANG An-ni, WU Xu-ling, LI Ya, HE Dian. LRRK2 gene mutation-associated semantic variant primary progressive aphasia: one case report and literatures review[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(6): 541-545.

https://journal11.magtechjournal.com/cjcnn/CN/Y2020/V20/I6/541

参考文献

[1] Mesulam MM. Primary progressive aphasia and the language network:the 2013 H. Houston Merritt Lecture[J]. Neurology, 2013, 81:456-462.
[2] Spinelli EG, Mandelli ML, Miller ZA, Santos-Santos MA, Wilson SM, Agosta F, Grinberg LT, Huang EJ, Trojanowski JQ, Meyer M, Henry ML, Comi G, Rabinovici G, Rosen HJ, Filippi M, Miller BL, Seeley WW, Gorno-Tempini ML. Typical and atypical pathology in primary progressive aphasia variants[J]. Ann Neurol, 2017, 81:430-443.
[3] Ji T, Ye S, Fan DS. Gene characteristics in frontotemporal dementia and its correlations with amyotrophic lateral sclerosis[J]. Zhonghua Nei Ke Za Zhi, 2017, 56:781-784.[冀拓, 叶珊, 樊东升. 额颞叶痴呆的致病基因特点及其与肌萎缩侧索硬化关系[J]. 中华内科杂志, 2017, 56:781-784.]
[4] Olszewska DA, Lonergan R, Fallon EM, Lynch T. Genetics of frontotemporal dementia[J]. Curr Neurol Neurosci Rep, 2016, 16:107.
[5] Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants[J]. Neurology, 2011, 76:1006-1014.
[6] Hales CM, Hu WT. From frontotemporal lobar degeneration pathology to frontotemporal lobar degeneration biomarkers[J]. Int Rev Psychiatry, 2013, 25:210-220.
[7] Bian H, Van Swieten JC, Leight S, Massimo L, Wood E, Forman M, Moore P, de Koning I, Clark CM, Rosso S, Trojanowski J, Lee VM, Grossman M. CSF biomarkers in frontotemporal lobar degeneration with known pathology[J]. Neurology, 2008, 70:1827-1835.
[8] Steinacker P, Hendrich C, Sperfeld AD, Jesse S, von Arnim CA, Lehnert S, Pabst A, Uttner I, Tumani H, Lee VM, Trojanowski JQ, Kretzschmar HA, Ludolph A, Neumann M, Otto M. TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis[J]. Arch Neurol, 2008, 65:1481-1487.
[9] Kuiperij HB, Versleijen AA, Beenes M, Verwey NA, Benussi L, Paterlini A, Binetti G, Teunissen CE, Raaphorst J, Schelhaas HJ, Küsters B, Pijnenburg YA, Ghidoni R, Verbeek MM. Tau rather than TDP-43 proteins are potential cerebrospinal fluid biomarkers for frontotemporal lobar degeneration subtypes:a pilot study[J]. J Alzheimers Dis, 2017, 55:585-595.
[10] Goossens J, Bjerke M, Van Mossevelde S, Van den Bossche T, Goeman J, De Vil B, Sieben A, Martin JJ, Cras P, De Deyn PP, Van Broeckhoven C, van der Zee J, Engelborghs S. Diagnostic value of cerebrospinal fluid tau, neurofilament, and progranulin in definite frontotemporal lobar degeneration[J]. Alzheimers Res Ther, 2018, 10:31.
[11] Goldman JS, Farmer JM, Wood EM, Johnson JK, Boxer A, Neuhaus J, Lomen-Hoerth C, Wilhelmsen KC, Lee VM, Grossman M, Miller BL. Comparison of family histories in FTLD subtypes and related tauopathies[J]. Neurology, 2005, 65:1817-1819.
[12] Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia[J]. Ann Neurol, 2006, 59:156-165.
[13] Rajput A, Dickson DW, Robinson CA, Ross OA, Dächsel JC, Lincoln SJ, Cobb SA, Rajput ML, Farrer MJ. Parkinsonism, LRRK2 G2019S, and tau neuropathology[J]. Neurology, 2006, 67:1506-1508.
[14] Guerreiro PS, Gerhardt E, Lopes da Fonseca T, Bähr M, Outeiro TF, Eckermann K. LRRK2 promotes tau accumulation, aggregation and release[J]. Mol Neurobiol, 2016, 53:3124-3135.
[15] Miklossy J, Qing H, Guo JP, Yu S, Wszolek ZK, Calne D, McGeer EG, McGeer PL. LRRK2 and chronic inflammation are linked to pallido-ponto-nigral degeneration caused by the N279K tau mutation[J]. Acta Neuropathol, 2007, 114:243-254.
[16] Nguyen APT, Daniel G, Valdés P, Islam MS, Schneider BL, Moore DJ. G2019S LRRK2 enhances the neuronal transmission of tau in the mouse brain[J]. Hum Mol Genet, 2018, 27:120-134.
[17] Bailey RM, Covy JP, Melrose HL, Rousseau L, Watkinson R, Knight J, Miles S, Farrer MJ, Dickson DW, Giasson BI, Lewis J. LRRK2 phosphorylates novel tau epitopes and promotes tauopathy[J]. Acta Neuropathol, 2013, 126:809-827.
[18] Sanchez-Contreras M, Heckman MG, Tacik P, Diehl N, Brown PH, Soto-Ortolaza AI, Christopher EA, Walton RL, Ross OA, Golbe LI, Graff-Radford N, Wszolek ZK, Dickson DW, Rademakers R. Study of LRRK2 variation in tauopathy:progressive supranuclear palsy and corticobasal degeneration[J]. Mov Disord, 2017, 32:115-123.
[19] Broce I, Karch CM, Wen N, Fan CC, Wang Y, Tan CH, Kouri N, Ross OA, Höglinger GU, Muller U, Hardy J, Momeni P, Hess CP, Dillon WP, Miller ZA, Bonham LW, Rabinovici GD, Rosen HJ, Schellenberg GD, Franke A, Karlsen TH, Veldink JH, Ferrari R, Yokoyama JS, Miller BL, Andreassen OA, Dale AM, Desikan RS, Sugrue LP. Immune-related genetic enrichment in frontotemporal dementia:an analysis of genome-wide association studies[J]. PLoS Med, 2018, 15:e1002487.
[20] Dächsel JC, Ross OA, Mata IF, Kachergus J, Toft M, Cannon A, Baker M, Adamson J, Hutton M, Dickson DW, Farrer MJ. LRRK2 G2019S substitution in frontotemporal lobar degeneration with ubiquitin-immunoreactive neuronal inclusions[J]. Acta Neuropathol, 2007, 113:601-606.
[21] Wider C, Dickson DW, Wszolek ZK. Leucine-rich repeat kinase 2 gene-associated disease:redefining genotype-phenotype correlation[J]. Neurodegener Dis, 2010, 7:175-179.

选择文件类型/文献管理软件名称

选择包含的内容

2 LRRK2基因突变相关语义变异型原发性进行性失语一例并文献复习

LRRK2 gene mutation-associated semantic variant primary progressive aphasia: one case report and literatures review

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	林丽, 崔珍珍, 何凡, 赵晓玲, 金丹群, 杨斌. IQSEC2基因变异致非典型Rett综合征并发育性癫痫性脑病四例遗传学特点分析[J]. 中国现代神经疾病杂志, 2024, 24(8): 674-683.
[2]	袁于青, 占青青, 谢亮. Ⅱ型亚历山大病一例[J]. 中国现代神经疾病杂志, 2024, 24(6): 502-506.
[3]	狄晓萌, 王佳伟, 段泽君, 刘磊. 脑脊液宏基因组学第二代测序辅助诊断中枢神经系统链球菌感染二例[J]. 中国现代神经疾病杂志, 2024, 24(4): 245-252.
[4]	徐金梅, 刘兵舰, 关鸿志, 单萍, 陈国华, 梅俊华. 重度发热伴血小板减少综合征脑炎一例[J]. 中国现代神经疾病杂志, 2024, 24(4): 253-257.
[5]	武倩, 詹飞霞, 曹立. TH基因变异致多巴反应性肌张力障碍二例[J]. 中国现代神经疾病杂志, 2024, 24(4): 285-289.
[6]	徐滢, 桂雅星. 脂质代谢异常对帕金森病进程的影响及临床意义[J]. 中国现代神经疾病杂志, 2024, 24(3): 131-138.
[7]	王晖, 俞萌, 吕鹤, 张巍, 袁云, 王朝霞. 以急性呼吸衰竭为主要表现的线粒体肌病一例[J]. 中国现代神经疾病杂志, 2023, 23(9): 821-825.
[8]	李萍, 徐艳芳, 胡帅, 曾晓霞, 漆学良. PSAT1基因变异致儿童期鱼鳞病合并青少年期周围神经病的磷酸丝氨酸氨基转移酶缺乏症一例[J]. 中国现代神经疾病杂志, 2023, 23(9): 826-831.
[9]	李冉, 邹慧敏, 邢春叶, 宋进, 郝延磊. GMPPB基因变异致肢带型肌营养不良合并先天性肌无力综合征一例[J]. 中国现代神经疾病杂志, 2023, 23(9): 832-837.
[10]	李海江, 王朝东. 以痉挛性截瘫为首发症状的早发型家族性阿尔茨海默病3型一家系（附点评）[J]. 中国现代神经疾病杂志, 2023, 23(9): 853-858.
[11]	任修德, 李涛, 范吉康, 王希森, 贾晓丹, 杨学军. 胶质母细胞瘤FGFR3-TACC3融合基因介导丙酮酸激酶M2入核促进DNA损伤修复基础研究[J]. 中国现代神经疾病杂志, 2023, 23(8): 745-757.
[12]	吴旭玲, 张安妮, 雷晓阳, 冯占辉, 王维, 贺电. 强直性肌营养不良症1型一例[J]. 中国现代神经疾病杂志, 2023, 23(8): 765-769.
[13]	李跃文, 褚先舟, 李娟, 秦艳, 吴桐, 陈先文. BSCL2基因c.455A>G突变致远端型遗传性运动神经病V型一家系[J]. 中国现代神经疾病杂志, 2023, 23(7): 643-647.
[14]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[15]	崔立立, 纪坤乾, 张正华, 张同霞, 赵玉英. 以排尿困难发病的SOD1基因变异致肌萎缩侧索硬化一例[J]. 中国现代神经疾病杂志, 2023, 23(5): 472-476.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 LRRK2基因突变相关语义变异型原发性进行性失语一例并文献复习

LRRK2 gene mutation-associated semantic variant primary progressive aphasia: one case report and literatures review

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价