NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease  

作　　者：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 

机构地区：[1]Department of Neurology,First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan,China [2]NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases,Zhengzhou,Henan,China [3]Department of Neurology,Xinxiang Medical University,Xinxiang,Henan,China

出　　处：《Stroke & Vascular Neurology》2023年第2期161-168,共8页卒中与血管神经病学（英文）

基　　金：supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences[grant number 2020-PT310-01];the National Natural Science Foundation of China to Dr.Chang-he Shi[grant number 82171247,81974211];the National Natural Science Foundation of China to Dr.Yu-ming Xu[grant numbers U1904207].

摘　　要：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.

关 键 词：PATIENTS CEREBRAL expanded 

分 类 号：R743[医药卫生—神经病学与精神病学]