Identification of Copy Number Variants as a Suspected Cause of Cerebral Small Vessel Disease
- 1Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT) Brisbane Queensland Australia
- 2Central Analytical Research Facility (CARF) Queensland University of Technology (QUT) Brisbane Queensland Australia
Abstract
Cerebral small vessel disease (CSVD) describes a range of neurological diseases affecting the small arteries, veins, and capillaries which supply the white matter and deep grey matter structures of the brain. They are the most common form of cerebrovascular disease, accounting for almost half of vascular dementia cases and approximately 20% of stroke incidence globally. Genetic testing is a routine diagnostic tool for monogenic CSVDs; however, less than 20% of patients have a causal variant in a known gene. Genetic testing for these disorders focuses on single nucleotide variants and short insertions or deletions, with larger genomic variation often unexplored as a cause of disease. In this study we performed whole‐exome sequencing (WES) on 111 patients suspected of familial CSVD that had previously tested negative for pathogenic variants in seven known CSVD genes (NOTCH3, HTRA1, COL4A1, COL4A2, TREX1, GLA, and FOXC1). Bioinformatic analysis of WES data, multiplex ligation‐dependent probe amplification, quantitative real‐time polymerase chain reaction assays, and Nanopore long‐read sequencing were used to identify suspected copy number variants. This work identified four candidate CNVs across NOTCH3, LMNB1, and COL4A2 which are potential causes of CSVD and highlights the need for further investigation of more complex forms of genetic variation and their potential roles as causal of CSVD.
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BibTeX
@article{guyler2026identification,
title = {{Identification of Copy Number Variants as a Suspected Cause of Cerebral Small Vessel Disease}},
author = {Solomon K. Guyler and Neven Maksemous and Rodney A. Lea and Robert A. Smith and Heidi G. Sutherland and Lyn R. Griffiths},
journal = {Clinical Genetics},
year = {2026},
month = aug,
doi = {10.1111/cge.70233},
url = {https://doi.org/10.1111/cge.70233},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Identification of Copy Number Variants as a Suspected Cause of Cerebral Small Vessel Disease
AU - Solomon K. Guyler
AU - Neven Maksemous
AU - Rodney A. Lea
AU - Robert A. Smith
AU - Heidi G. Sutherland
AU - Lyn R. Griffiths
PY - 2026
DA - 2026/08/27
JO - Clinical Genetics
DO - 10.1111/cge.70233
UR - https://doi.org/10.1111/cge.70233
AB - Cerebral small vessel disease (CSVD) describes a range of neurological diseases affecting the small arteries, veins, and capillaries which supply the white matter and deep grey matter structures of the brain. They are the most common form of cerebrovascular disease, accounting for almost half of vascular dementia cases and approximately 20% of stroke incidence globally. Genetic testing is a routine diagnostic tool for monogenic CSVDs; however, less than 20% of patients have a causal variant in a known gene. Genetic testing for these disorders focuses on single nucleotide variants and short insertions or deletions, with larger genomic variation often unexplored as a cause of disease. In this study we performed whole‐exome sequencing (WES) on 111 patients suspected of familial CSVD that had previously tested negative for pathogenic variants in seven known CSVD genes (NOTCH3, HTRA1, COL4A1, COL4A2, TREX1, GLA, and FOXC1). Bioinformatic analysis of WES data, multiplex ligation‐dependent probe amplification, quantitative real‐time polymerase chain reaction assays, and Nanopore long‐read sequencing were used to identify suspected copy number variants. This work identified four candidate CNVs across NOTCH3, LMNB1, and COL4A2 which are potential causes of CSVD and highlights the need for further investigation of more complex forms of genetic variation and their potential roles as causal of CSVD.
SN - 0009-9163
SN - 1399-0004
ER -