特发性震颤患者NOTCH2NLC基因动态突变筛查

doi:10.16352/j.issn.1001-6325.2023.12.1778

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (12): 1778-1783.doi: 10.16352/j.issn.1001-6325.2023.12.1778

特发性震颤患者NOTCH2NLC基因动态突变筛查

张忻怡¹, 赵熙萌¹, 杨英麦², 万新华², 崔丽英², 张学¹, 柳青^2*

1.中国医学科学院基础医学研究所北京协和医学院基础学院麦库西克-张孝骞协和遗传医学中心疑难重症及罕见病国家重点实验室,北京 100005;
2.中国医学科学院北京协和医学院北京协和医院神经内科, 北京 100730

收稿日期:2023-09-08 修回日期:2023-10-25 出版日期:2023-12-05 发布日期:2023-11-29
通讯作者: ^* liuqingpumch@126.com
基金资助:
国家重点研发计划项目(2022YFC2703900,2022YFC2703903);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-018,2022-I2M-JB-004);国家自然科学基金(81788101)

Screening for NOTCH2NLC gene dynamic mutation in patients with essential tremor

ZHANG Xinyi¹, ZHAO Ximeng¹, YANG Yingmai², WAN Xinhua², CUI Liying², ZHANG Xue¹, LIU Qing^2*

1. McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. Department of Neurology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China

Received:2023-09-08 Revised:2023-10-25 Online:2023-12-05 Published:2023-11-29
Contact: ^* liuqingpumch@126.com

摘要/Abstract

摘要： 目的对110例特发性震颤(ET)患者进行致病基因变异鉴定。方法收集在北京协和医院神经内科就诊的110例ET患者的临床资料并采集外周血,从患者外周血中提取基因组DNA。通过三引物PCR(TP-PCR)对ET患者进行NOTCH2NLC动态突变检测,由于ET与多种神经变性病机制相关,因此通过定制的二代测序筛查子组(panel)对神经退行性疾病相关基因的罕见变异进行筛查。结果在110例ET患者队列和187名匹配的对照个体中,ET患者组发病年龄为(36.30±17.64)岁,有家族病史者占74.8%。未发现NOTCH2NLC异常三核苷酸重复扩增,ET患者(GGC)n重复次数在10~47(平均18.6±5.4)次内。变异负荷分析显示ET与PLA2G6罕见变异有相关性;在4例PLA2G6患者中发现了3个罕见的意义未明变异。结论 NOTCH2NLC动态突变在ET患者中罕见,提示需要筛选ET多重发病机制。

关键词: 特发性震颤, NOTCH2NLC, 遗传筛查

Abstract: Objective To identify the pathogenic variants in 110 patients with essential tremor (ET). Methods Clinical data and peripheral blood samples of ET patients were collected from the Department of Neurology of Peking Union Medical College Hospital and then the genomic DNA was extracted. Dynamic mutation detection of NOTCH2NLC was performed in patients with essential tremor by triplet repeat primed PCR(TP-PCR). Since ET is associated with multiple mechanisms of neuro-degeneration, the next generation sequencing (NGS) panel targeting neurodegenerative associating genes were performed to check pathogenic variants in additional genes. Results A total of 110 ET patients and 187 matched control individuals were recruited. The age of onset in the current ET group was (36.30±17.64)years, and 74.8% patients had a family history. No abnormal trinucleotide repeat expansion in NOTCH2NLC was identified. The repeat number of (GGC)n lied within normal ranges between 10-47 (average 18.6±5.4). Variants burden analysis showed association of ET with PLA2G6. Three rare variants in four patients in PLA2G6 were identified with unknown significance. Conclusions Dynamic mutations of NOTCH2NLC are uncommon in ET patients and that suggests need of more researches for further exploring the genetic mechanism of ET.

Key words: essential tremor, NOTCH2NLC, genetic screening

中图分类号:

R742

张忻怡, 赵熙萌, 杨英麦, 万新华, 崔丽英, 张学, 柳青. 特发性震颤患者NOTCH2NLC基因动态突变筛查[J]. 基础医学与临床, 2023, 43(12): 1778-1783.

ZHANG Xinyi, ZHAO Ximeng, YANG Yingmai, WAN Xinhua, CUI Liying, ZHANG Xue, LIU Qing. Screening for NOTCH2NLC gene dynamic mutation in patients with essential tremor[J]. Basic & Clinical Medicine, 2023, 43(12): 1778-1783.

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特发性震颤患者NOTCH2NLC基因动态突变筛查

Screening for NOTCH2NLC gene dynamic mutation in patients with essential tremor

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