Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
    • Education
  • Online Sections
    • COVID-19
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • Topics A-Z
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
    • Education
  • Online Sections
    • COVID-19
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • Topics A-Z
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

Share

January 07, 2020; 94 (1) Article

NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population

Yi-Chung Lee, Chih-Ping Chung, Ming-Hong Chang, Shuu-Jiun Wang, Yi-Chu Liao
First published December 2, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008700
Yi-Chung Lee
From the Department of Neurology (Y.-C. Lee, C.-P.C., S.-J.W., Y.-C. Liao), Taipei Veterans General Hospital; Department of Neurology (Y.-C. Lee, C.-P.C., M.-H.C., S.-J.W., Y.-C. Liao) and Brain Research Center (Y.-C. Lee, S.-J.W., Y.-C. Liao), National Yang-Ming, University School of Medicine, Taipei; and Department of Neurology (M.-H.C.), Taichung Veterans General Hospital, Taiwan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chih-Ping Chung
From the Department of Neurology (Y.-C. Lee, C.-P.C., S.-J.W., Y.-C. Liao), Taipei Veterans General Hospital; Department of Neurology (Y.-C. Lee, C.-P.C., M.-H.C., S.-J.W., Y.-C. Liao) and Brain Research Center (Y.-C. Lee, S.-J.W., Y.-C. Liao), National Yang-Ming, University School of Medicine, Taipei; and Department of Neurology (M.-H.C.), Taichung Veterans General Hospital, Taiwan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ming-Hong Chang
From the Department of Neurology (Y.-C. Lee, C.-P.C., S.-J.W., Y.-C. Liao), Taipei Veterans General Hospital; Department of Neurology (Y.-C. Lee, C.-P.C., M.-H.C., S.-J.W., Y.-C. Liao) and Brain Research Center (Y.-C. Lee, S.-J.W., Y.-C. Liao), National Yang-Ming, University School of Medicine, Taipei; and Department of Neurology (M.-H.C.), Taichung Veterans General Hospital, Taiwan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuu-Jiun Wang
From the Department of Neurology (Y.-C. Lee, C.-P.C., S.-J.W., Y.-C. Liao), Taipei Veterans General Hospital; Department of Neurology (Y.-C. Lee, C.-P.C., M.-H.C., S.-J.W., Y.-C. Liao) and Brain Research Center (Y.-C. Lee, S.-J.W., Y.-C. Liao), National Yang-Ming, University School of Medicine, Taipei; and Department of Neurology (M.-H.C.), Taichung Veterans General Hospital, Taiwan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi-Chu Liao
From the Department of Neurology (Y.-C. Lee, C.-P.C., S.-J.W., Y.-C. Liao), Taipei Veterans General Hospital; Department of Neurology (Y.-C. Lee, C.-P.C., M.-H.C., S.-J.W., Y.-C. Liao) and Brain Research Center (Y.-C. Lee, S.-J.W., Y.-C. Liao), National Yang-Ming, University School of Medicine, Taipei; and Department of Neurology (M.-H.C.), Taichung Veterans General Hospital, Taiwan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Short Form
Citation
NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population
Yi-Chung Lee, Chih-Ping Chung, Ming-Hong Chang, Shuu-Jiun Wang, Yi-Chu Liao
Neurology Jan 2020, 94 (1) e87-e96; DOI: 10.1212/WNL.0000000000008700

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
256

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Objective To test the hypothesis that the prevalence and clinical effect of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been underestimated in Asian populations.

Methods The Taiwan Biobank, containing 1,517 Taiwanese genome sequences, was queried for pathogenic NOTCH3 cysteine-altering mutations. NOTCH3 mutations identified in the reference population were genotyped in 7,038 stroke- and dementia-free individuals and 800 patients with ischemic stroke. NOTCH3 genotyping, clinical manifestations, and the severity of white matter lesions on MRI were compared between the 2 groups.

Results Three cysteine-altering NOTCH3 variants (p.R544C, p.C853Y, and p.C884Y) were identified from the Taiwan Biobank. We confirmed that the NOTCH3 p.R544C mutation was present in a significant number of individuals in Taiwan, including 60 of the 7,038 healthy controls (0.9%), 17 of the 800 patients with ischemic stroke (2.1%), and 16 of the 245 patients with small vessel occlusion (SVO) stroke (6.5%). The other 2 cysteine-altering mutations were rarely detected. After adjusting for vascular risk factors, harboring the p.R544C variant resulted in a 3.40-fold increased risk for overall stroke and an 11.05-fold increased risk for SVO stroke (p = 0.0001 and 3.9 × 10−10, respectively). Three symptom-free individuals carrying the p.R544C mutation had extensive leukoencephalopathy typical of CADASIL at age 59, 66, and 67, suggesting that p.R544C-related CADASIL could remain subclinical at advanced age.

Conclusion The NOTCH3 p.R544C variant is an important risk factor for SVO stroke in Taiwan. Phenotypic variation among individuals carrying a NOTCH3 mutation indicates the existence of disease-modifying factors in CADASIL.

Glossary

CADASIL=
cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy;
CI=
confidence interval;
EGFR=
epidermal growth factor–like repeat;
ExAC=
exome aggregation consortium;
OR=
odds ratio;
SVO=
small vessel occlusion;
TC-VGH=
Taichung Veterans General Hospital;
TP-VGH=
Taipei Veterans General Hospital;
WML=
white matter lesion

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 17, 2019.
  • Accepted in final form June 27, 2019.
  • © 2019 American Academy of Neurology
View Full Text

AAN Members

We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.

Google Safari Microsoft Edge Firefox

Click here to login

AAN Non-Member Subscribers

Click here to login

Purchase access

For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)

Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here 

Purchase
Individual access to articles is available through the Add to Cart option on the article page.  Access for 1 day (from the computer you are currently using) is US$ 39.00.  Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means.  The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use.  Distributing copies (electronic or otherwise) of the article is not allowed.

Disputes & Debates: Rapid online correspondence

  • Reader response: NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population
    • Xingshun Xu, Neurologist, Department of Neurology, the First Affiliated Hospital of Soochow University
    • Miao Sun, Genetic scientist, Institute of Fetology, the First Affiliated Hospital of Soochow University
    Submitted January 11, 2020
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Related Articles

  • No related articles found.

Topics Discussed

  • All Cerebrovascular disease/Stroke
  • CADASIL
  • Risk factors in epidemiology

Alert Me

  • Alert me when eletters are published
Neurology: 98 (21)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • Neurology: Education
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2022 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise