Abstract WMP102: Prevalence Of Genetic Mutations In 15 Mendelian Stroke Genes In Young Stroke Patients

Abstract

Introduction: Although the heritability of stroke might be higher in young-age stroke population, it is even uncertain how many of them has monogenic causes of stroke. We aimed to estimate the prevalence and clinical characteristics of 15 monogenic disorders associated with stroke in a large, unselected young-age stroke population Methods: From a prospective, nationwide, multicenter, acute stroke registry of consecutive patients admitted to 15 academic or regional stroke centers in Korea, we enrolled all patients aged 55 years or younger except those who refuse to participate in this study. We performed genetic analysis using a customized targeted next-generation sequencing panel ( GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP ) to find clinically relevant genetic variants, and reviewed clinical information of the patients. Results: Genetic analysis was performed in 1,033 patients (male 70.7%, mean age 45.8±7.9). Twenty-eight clinically relevant genetic variants were identified in 131 (12.7%) patients, and were found most frequently in RNF213 (59, 5.7%) followed by ABCC6 (53, 5.1%) and NOTCH3 (15, 1.5%). Genetic variants were more commonly observed in younger group than older group (17.1% vs. 9.3%, p=0.021), but were not different according to vascular risk factor burden. Patients with premature (<60y) family history of stroke had genetic variants more frequently than those with family history at ≥60y (23.7% vs. 11.4%, p=0.047). Typical neuroimaging abnormalities were observed in only 25% of patients with RNF213 variants and 27% of those with NOTCH3 variants. Variants of uncertain significance were found in 15.4%. Conclusion: Clinically relevant genetic variants were not uncommon than expected. We might have opportunities to improve our daily practice by genetic counseling patients and their families to reduce the future stroke.