RT Journal Article SR Electronic T1 NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease JF Stroke and Vascular Neurology JO Stroke Vasc Neurol FD BMJ Publishing Group Ltd SP svn-2022-001631 DO 10.1136/svn-2022-001631 A1 Yun-chao Wang A1 Yu Fan A1 Wen-Kai Yu A1 Si Shen A1 Jia-Di Li A1 Yuan Gao A1 Yan Ji A1 Yu-Sheng Li A1 Lu-Lu Yu A1 Zi-Chen Zhao A1 Shan-Shan Li A1 Yao Ding A1 Chang-He Shi A1 Yu-ming Xu YR 2022 UL http://svn.bmj.com/content/early/2022/10/07/svn-2022-001631.abstract AB 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.All data relevant to the study are included in the article or uploaded as supplementary information.