Rare Variants of Monogenic Cerebral Small Vessel Diseases -Related Genes: A Study in a Cohort of Patients with Cerebral Small Vessel Diseases
10.12376/j.issn.2097-0501.2022.02.008
- VernacularTitle:基于脑小血管病队列的单基因遗传性脑小血管病致病基因低频有害变异的研究
- Author:
Mengyao WAN
1
;
Jingyi LIU
2
,
3
;
Yicheng ZHU
3
,
4
;
Lixin ZHOU
3
,
4
;
Jun NI
3
,
4
;
Bin PENG
3
,
4
;
Ming YAO
3
,
4
Author Information
1. Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
2. Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &
3. Peking Union Medical College, Beijing 100730, China.
4. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &
- Publication Type:Journal Article
- Keywords:
cerebral small vessel diseases;
monogenic cerebral small vessel diseases;
sporadic cerebral small vessel diseases;
low-frequency mutation;
NOTCH3;
HTRA1
- From:
JOURNAL OF RARE DISEASES
2022;1(2):142-150
- CountryChina
- Language:Chinese
-
Abstract:
Objective This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance. Methods This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers. Results A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers. Conclusions The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.
