Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 6;7(6):e639.
doi: 10.1212/NXG.0000000000000639. eCollection 2021 Dec.

Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population

Chul-Hoo Kang  1 , Young Mee Kim  1 , Yang-Ji Kim  1 , Su-Jeong Hong  1 , Do Yoon Kim  1 , Hyun Goo Woo  1 , Young Ree Kim  1 , Joong-Goo Kim  1 , Jung Seok Lee  1 , Mi Hee Kong  1 , Hyeon Ju Kim  1 , Jay Chol Choi  1
Affiliations

Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population

Chul-Hoo Kang et al. Neurol Genet. .

Abstract

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.

PubMed Disclaimer

Figures

Figure
Figure. Brain MRI of the 2 Individuals With p.Arg544Cys Variants
Patient 2 is a 58-year-old man who had had an abrupt onset of mild dysarthria at age 54 years. Diffusion MRI at that time showed a small subacute infarction on the left frontal white matter (arrow) and multiple small white matter hyperintensity lesions on fluid attenuated inversion recovery images. Patient 3 is a 50-year-old man and received a brain MRI examination as a screening health checkup and had a few small subcortical white matter hyperintensity lesions and periventricular white matter lesions.
See this image and copyright information in PMC

References

    1. Choi JC. Genetics of cerebral small vessel disease. J Stroke. 2015;17(1):7-16. - PMC - PubMed
    1. Narayan SK, Gorman G, Kalaria RN, Ford GA, Chinnery PF. The minimum prevalence of CADASIL in northeast England. Neurology. 2012;78(13):1025-1027. - PMC - PubMed
    1. Rutten JW, Dauwerse HG, Gravesteijn G, et al. . Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol. 2016;3(11):844-853. - PMC - PubMed
    1. Jeon S, Bhak Y, Choi Y, et al. . Korean genome project: 1094 Korean personal genomes with clinical information. Sci Adv. 2020;6(22):eaaz7835. - PMC - PubMed
    1. Jung KS, Hong KW, Jo HY, et al. . KRGDB: the large-scale variant database of 1722 Koreans based on whole genome sequencing. Database. 2020;2020:baz146 doi: 10.1093/database/baz146. Published: March 4, 2020. - DOI - PMC - PubMed