Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Specialty Sites
    • COVID-19
    • Practice Current
    • Practice Buzz
    • Without Borders
    • Equity, Diversity and Inclusion
    • Innovations in Care Delivery
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • 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
  • Specialty Sites
    • COVID-19
    • Practice Current
    • Practice Buzz
    • Without Borders
    • Equity, Diversity and Inclusion
    • Innovations in Care Delivery
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • 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

July 19, 2016; 87 (3) Article

Huntington disease reduced penetrance alleles occur at high frequency in the general population

Chris Kay, Jennifer A. Collins, Zosia Miedzybrodzka, Steven J. Madore, Erynn S. Gordon, Norman Gerry, Mark Davidson, Ramy A. Slama, Michael R. Hayden
First published June 22, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002858
Chris Kay
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer A. Collins
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zosia Miedzybrodzka
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven J. Madore
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erynn S. Gordon
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norman Gerry
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Davidson
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ramy A. Slama
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael R. Hayden
From the Centre for Molecular Medicine and Therapeutics (C.K., J.A.C., R.A.S., M.R.H.), University of British Columbia, Canada; Medical Genetics Group (Z.M., M.D.), School of Medicine and Dentistry, University of Aberdeen, UK; and Molecular Biology Group (S.J.M., E.S.G., N.G.), Coriell Institute for Medical Research, Camden, NJ.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Huntington disease reduced penetrance alleles occur at high frequency in the general population
Chris Kay, Jennifer A. Collins, Zosia Miedzybrodzka, Steven J. Madore, Erynn S. Gordon, Norman Gerry, Mark Davidson, Ramy A. Slama, Michael R. Hayden
Neurology Jul 2016, 87 (3) 282-288; DOI: 10.1212/WNL.0000000000002858

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
832

Share

  • Article
  • Figures & Data
  • Info & Disclosures
  • CME Course
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 directly estimate the frequency and penetrance of CAG repeat alleles associated with Huntington disease (HD) in the general population.

Methods: CAG repeat length was evaluated in 7,315 individuals from 3 population-based cohorts from British Columbia, the United States, and Scotland. The frequency of ≥36 CAG alleles was assessed out of a total of 14,630 alleles. The general population frequency of reduced penetrance alleles (36–39 CAG) was compared to the prevalence of patients with HD with genetically confirmed 36–39 CAG from a multisource clinical ascertainment in British Columbia, Canada. The penetrance of 36–38 CAG repeat alleles for HD was estimated for individuals ≥65 years of age and compared against previously reported clinical penetrance estimates.

Results: A total of 18 of 7,315 individuals had ≥36 CAG, revealing that approximately 1 in 400 individuals from the general population have an expanded CAG repeat associated with HD (0.246%). Individuals with CAG 36–37 genotypes are the most common (36, 0.096%; 37, 0.082%; 38, 0.027%; 39, 0.000%; ≥40, 0.041%). General population CAG 36–38 penetrance rates are lower than penetrance rates extrapolated from clinical cohorts.

Conclusion: HD alleles with a CAG repeat length of 36–38 occur at high frequency in the general population. The infrequent diagnosis of HD at this CAG length is likely due to low penetrance. Another important contributing factor may be reduced ascertainment of HD in those of older age.

GLOSSARY

CI=
confidence interval;
CPMC=
Coriell Personalized Medicine Collaborative;
HD=
Huntington disease;
IRB=
institutional review board;
UBC C&W CREB=
University of British Columbia Children's and Women's Health Centre Clinical Research Ethics Board

Footnotes

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

  • Editorial, page 247

  • Received September 15, 2015.
  • Accepted in final form March 16, 2016.
  • © 2016 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

  • Author Response Re: Huntington Disease: Intermediate CAG Repeats
    • Michael R. Hayden, Killam Professor of Medical Genetics, University of British Columbiamrh@cmmt.ubc.ca
    • Chris Kay, Vancouver, Canada
    Submitted October 17, 2016
  • Huntington disease: Intermediate CAG repeats
    • Joseph Jankovic, Professor of Neurology, Baylor College of Medicinejosephj@bcm.edu
    • F. Squitieri, MD, PhD; Rome, Italy
    Submitted July 20, 2016
Comment

NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.

  • Stay timely. 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.
  • 200 words maximum.
  • 5 references maximum. Reference 1 must be the article on which you are commenting.
  • 5 authors maximum. Exception: replies can include all original authors of the article.
  • 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 Disputes & Debates Submission 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
    • AUTHOR CONTRIBUTIONS
    • STUDY FUNDING
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Disclosures
  • CME Course

More Online

CME Course

Related Articles

  • Huntington diseaseMore common than you think?

Topics Discussed

  • All epidemiology
  • All Genetics
  • Huntington's disease

Alert Me

  • Alert me when eletters are published
Neurology: 96 (15)

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
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

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

© 2021 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise