Related Experiment Video
Updated: Mar 31, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
SAMHD1 Gene Mutations Are Associated with Cerebral Large-Artery Atherosclerosis
Wei Li1, Baozhong Xin2, Junpeng Yan3
1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China ; China National Clinical Research Centre for Neurological Diseases, Centre of Stroke, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing 100050, China.
Insights
SAMHD1 gene mutations are linked to an increased stroke risk, particularly in large-artery atherosclerosis. These mutations impair protein function, suggesting a genetic predisposition to cerebrovascular disease.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Cerebrovascular diseases, including stroke, represent a significant global health burden.
- The role of specific gene mutations in the general population's susceptibility to stroke requires further investigation.
Purpose of the Study:
- To determine if mutations in the SAMHD1 gene are associated with cerebrovascular disease in a Chinese population.
- To analyze the functional impact of identified SAMHD1 mutations on protein activity and stability.
Main Methods:
- Genomic DNA sequencing of the SAMHD1 gene in 300 patients (100 with large-artery atherosclerosis (LAA), 100 with small vessel disease (SVD), and 100 controls).
- In vitro expression and purification of wild-type and mutant SAMHD1 proteins.
- Assays to evaluate the dNTPase activity and tetramer formation of SAMHD1 proteins.
Main Results:
- Three heterozygous SAMHD1 mutations (two missense, one splice site) were identified in 3% of the LAA group.
- No SAMHD1 mutations were detected in the SVD or control groups.
- Mutant SAMHD1 proteins exhibited impaired dNTPase activity and reduced tetramer stability.
Conclusions:
- Heterozygous SAMHD1 mutations may contribute to a genetic predisposition for stroke, potentially interacting with other risk factors.
- The findings highlight SAMHD1 as a potential genetic factor influencing cerebrovascular disease risk.
Background:
To investigate whether one or more SAMHD1 gene mutations are associated with cerebrovascular disease in the general population using a Chinese stroke cohort.
Methods:
Patients with a Chinese Han background (N = 300) diagnosed with either cerebral large-artery atherosclerosis (LAA, n = 100), cerebral small vessel disease (SVD, n = 100), or other stroke-free neurological disorders (control, n = 100) were recruited. Genomic DNA from the whole blood of each patient was isolated, and direct sequencing of the SAMHD1 gene was performed. Both wild type and mutant SAMHD1 proteins identified from the patients were expressed in E. coli and purified; then their dNTPase activities and ability to form stable tetramers were analysed in vitro.
Results:
Three heterozygous mutations, including two missense mutations c.64C>T (P22S) and c.841G>A (p.E281K) and one splice site mutation c.696+2T>A, were identified in the LAA group with a prevalence of 3%. No mutations were found in the patients with SVD or the controls (p = 0.05). The mutant SAMHD1 proteins were functionally impaired in terms of their catalytic activity as a dNTPase and ability to assemble stable tetramers.
Conclusions:
Heterozygous SAMHD1 gene mutations might cause genetic predispositions that interact with other risk factors, resulting in increased vulnerability to stroke.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:39Mutations
01:11Genetic Lingo
01:30Coronary Artery Disease I: Introduction