Monogenic basis of young-onset cryptogenic stroke: a multicenter study

作者：Weizhuang Yuan, Liang Shang, Dai‐Shi Tian, Shiwen Wu, Yong You, Chenglin Tian, Bo Wu, Jun Liu, Qinjian Sun, Qing Liu, Weihai Xu · 发表于：Annals of Translational Medicine · 年份：2022 · DOI：10.21037/atm-21-3843 · 被引用次数：7 · 研究领域：Connective tissue disorders research、Skin and Cellular Biology Research、Oropharyngeal Anatomy and Pathologies

Background: The prevalence of stroke in young adults is increasing. We investigated the monogenic basis of young adult cryptogenic stroke patients. Methods: This multicenter study enrolled cryptogenic stroke patients under 55 years old, and individuals with nonstroke diseases were included as controls. Targeted next-generation sequencing (NGS) was applied with a custom-designed gene panel that included 551 genes. Rare variants were classified into 2 groups: pathogenic variants and variants of unknown significance. Results: A total of 153 individuals, including 30 (21 males, 70%; mean age 36.1±10.2 years) in the disease group and 123 (59 males, 48.0%; mean age 40.4±13.1 years) in the control group, were recruited. In the disease group, 32 rare variants were identified. Among these individuals, 18 pathogenic variants in 16 patients were detected, with a 53.3% (16/30) diagnostic yield of monogenic causes for cryptogenic stroke. None of these mutations were observed in the control group. Among the mutant genes, the most prevalent were Notch receptor 3 (NOTCH3), protein kinase AMP-activated noncatalytic subunit gamma 2 (PRKAG2), and ryanodine receptor 2 (RYR2). Genes associated with cardiogenic diseases showed the highest mutation frequency (10/18, 55.6%) followed by genes associated with small-vessel diseases (SVDs) and coagulation disorders. None of the patients with mutations had evident abnormalities in the heart or other systems checked by routine tests. For the imaging pheno...