Abstract Details

Title Pattern of Neuroimaging Markers Related to Cerebral Small Vessel Disease in Carriers of Rare Deleterious Variants

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S2 - Advances in Stroke Imaging and Biomarkers (1:48 PM-2:00 PM)

Poster/Presentation
Number 004

Background Previous studies reported that rare deleterious variants are associated with a heavy burden of cerebral small vessel disease (CSVD) in the general population while the patterns of imaging markers remain uncovered.

Objective This study aimed to determine the associations of rare deleterious variants with imaging markers in a large multicenter CSVD cohort.

Design/Methods As part of a multicenter, prospective cohort, we included participants with complete brain magnetic resonance imaging (MRI) and whole-exome sequencing in analysis. 11 variants (NOTCH3, HTRA1, COL4A1, COL4A2, CTSA, GAL, TREX1, CTC1, APP, GSN, ADA2) with minor allele frequency <1% in all 4 public population databases were defined as rare deleterious variants. We used wilcoxon rank sum test to compare the patterns of imaging markers, including white matter hyperintensity (WMH), silent brain infarcts (SBIs), and cerebral microbleed (CMB), between rare deleterious variant carriers and noncarriers.

Results A total of 623 participants were included in analysis, among whom 232(37.24%) carried rare deleterious variants, with 111(17.82%) carrying rare NOTCH3 variants and 33(5.30%), 28(4.49%), 25(4.01%), 18(2.89%), 18(2.89%) carrying rare HTRA1, GSN, COL4A2, CTC1, APP variants, respectively. Compared with participants without any rare deleterious variant, rare NOTCH3 variants carriers had higher number of SBIs with a preferable distribution in basal ganglia and brainstem. In subgroup analysis, a higher number of SBIs was found in the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants carriers, but not in carriers of EGFr-sparing rare NOTCH3 variants. Rare HTRA1 and GAL variants carriers presented a heavier burden of WMH involving both periventricular and subcortical area. Rare TREX1, COL4A1, COL4A2, CTSA, and CTC1 variants carriers were found to have a higher load of CMBs.

Conclusions Individuals with rare deleterious variants have a distinct pattern of MRI imaging markers related to CSVD. Carriers of rare deleterious variants may be genetically predisposed to age-related CSVD.

Authors/Disclosures
Chengqian Li, MD, PhD (Peking Union Medical College Hospital) PRESENTER	Dr. Li has nothing to disclose.
Ming Yao	Ming Yao has nothing to disclose.
Mengyao Wan (Peking Union Medical College)	Miss Wan has nothing to disclose.
Jingyi Liu, MD (Peking Union Medical College Hospital)	Dr. Liu has nothing to disclose.
Zi-Yue Liu	Zi-Yue Liu has nothing to disclose.
Fei Han	Fei Han has nothing to disclose.
Lixin Zhou	Lixin Zhou has nothing to disclose.
Jun Ni	Jun Ni has nothing to disclose.
Yi-Cheng Zhu, MD, PhD (Peking Union Medical College Hospital)	Dr. Zhu has nothing to disclose.

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