遺伝性脳小血管病のスクリーニングのための遺伝子パネルアプローチ：概念実証研究

Background: The predictive performance of pre-screening phenotype-based algorithms in selecting patients with cerebral small vessel disease (cSVD), one of the main causes of ischaemic and haemorrhagic stroke and dementia, more likely to harbor clinically relevant genetic variants (CRGVs) has to date been poorly defined, making it a clinical challenge to decide which patients to screen for hereditary cSVD (hcSVD). Methods: We designed a high-throughput gene panel to identify variants in 27 candidate genes associated with cSVD and screened patients selected by a specific phenotype-based algorithm at one comprehensive stroke center from 2020 to 2023. We categorized participants into two sub-groups defined by pre-screening likelihood of hcSVD (hcSVD; High-Probability Group, HPG vs. Low-Probability Group, LPG) and compared the results of molecular analysis. Results: Among 65 probands, we detected four (6.1%) pathogenic CRGVs and seven (10.7%) variants of unknown significance (VUSs) in 11 (16.9%) patients. Pathogenic CRGVs were exclusively detected in the HPG (4/22 probands), corresponding to an 18.2% prevalence of hcSVD in this group. Of the seven VUSs, five (22.7%) were detected in the HPG vs. two (4.6%) in the LPG. Conclusions: The pragmatic algorithm we are proposing has the potential to help clinicians in identifying patients who are more likely to harbor monogenic disease.