<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.

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

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

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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

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