NOTCH2NLC在脑血管疾病患者中扩增GGC重复序列。

IF 4.4 1区 医学 Q1 CLINICAL NEUROLOGY Stroke and Vascular Neurology Pub Date : 2023-04-01 DOI:10.1136/svn-2022-001631
Yun-Chao Wang, Yu Fan, Wen-Kai Yu, Si Shen, Jia-Di Li, Yuan Gao, Yan Ji, Yu-Sheng Li, Lu-Lu Yu, Zi-Chen Zhao, Shan-Shan Li, Yao Ding, Chang-He Shi, Yu-Ming Xu
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引用次数: 4

摘要

目的:人类特异性NOTCH2NLC基因的GGC重复扩增已被报道为神经元核内包涵病(NIID)的原因。鉴于NIID与脑血管病(CSVD)认知功能障碍的临床重叠,两种疾病在脑MRI t2 -液体衰减反转恢复序列上均表现为白质高信号,白质高信号是CSVD的主要神经影像学标志物。因此,我们假设GGC重复扩增也可能导致CSVD。为了进一步研究NOTCH2NLC GGC重复扩增与CSVD之间的关系,我们对814例CSVD患者进行了遗传分析。方法:我们对814例散发性CSVD患者的NOTCH2NLC进行了全面的GGC重复扩展筛查。他们的法泽卡得分大于等于3分。重复引物PCR和荧光扩增子长度分析用于鉴定GGC重复扩增,全外显子组测序用于检测先前报道的与CSVD相关基因的任何致病性突变。结果:我们发现9例(1.11%)患者具有致病性GGC重复扩增,范围从41到98个重复。NOTCH2NLC扩增GGC重复序列的次要等位基因频率为0.55%。结论:我们的研究结果表明,NOTCH2NLC中中长度和较长长度的GGC重复扩增与散发性CSVD有关。这为研究心血管疾病的发病机制提供了新的思路。
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NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease.

Objective: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease.

Methods: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.

Results: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.

Conclusion: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.

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来源期刊
Stroke and Vascular Neurology
Stroke and Vascular Neurology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
11.20
自引率
1.70%
发文量
63
审稿时长
15 weeks
期刊介绍: Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.
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