RT Journal Article SR Electronic T1 Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e639 DO 10.1212/NXG.0000000000000639 VO 7 IS 6 A1 Kang, Chul-Hoo A1 Kim, Young Mee A1 Kim, Yang-Ji A1 Hong, Su-Jeong A1 Kim, Do Yoon A1 Woo, Hyun Goo A1 Kim, Young Ree A1 Kim, Joong-Goo A1 Lee, Jung Seok A1 Kong, Mi Hee A1 Kim, Hyeon Ju A1 Choi, Jay Chol YR 2021 UL http://ng.neurology.org/content/7/6/e639.abstract AB Objective This study aimed to determine the frequency of pathogenic NOTCH3 variants among Koreans.Methods In this cross-sectional study, we queried for pathogenic NOTCH3 variants in 2 Korean public genome databases: the Korean Reference Genome Database (KRGDB) and the Korean Genome Project (Korea1K). In addition, we screened the 3 most common pathogenic NOTCH3 variants (p.Arg75Pro, p.Arg544Cys, and p.Arg578Cys) for 1,000 individuals on Jeju Island, where the largest number of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported in Korea.Results The pathogenic NOTCH3 variant (p.Arg544Cys) was found in 0.12% of sequences in the KRGDB, and 3 pathogenic variants (p.Arg75Pro, p.Arg182Cys, and p.Arg544Cys) were present in 0.44% of the Korea1K database. Of the 1,000 individuals on Jeju Island, we found 2 cysteine-altering NOTCH3 variants (p.Arg544Cys variant in 9 and p.Arg578Cys in 1 individual) in 1.00% of the participants (95% confidence interval: 0.48%–1.83%). The presence of cysteine-altering NOTCH3 variants was significantly associated with a history of stroke (p < 0.001).Discussion Pathogenic NOTCH3 variants are frequently found in the general Korean population. Such a high prevalence of pathogenic variants could threaten the brain health of tens of thousands to hundreds of thousands of older adults in Korea.