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

Share

April 18, 2017; 88 (16 Supplement) April 27, 2017

Genetic markers of myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) in human urine (S42.005)

Layal Antoury, Ningyan Hu, Leonora Balaj, Xandra Breakefield, Thurman Wheeler
First published April 17, 2017,
Layal Antoury
1Neurology, Massachusetts General Hospital Boston MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ningyan Hu
1Neurology, Massachusetts General Hospital Boston MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leonora Balaj
1Neurology, Massachusetts General Hospital Boston MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xandra Breakefield
1Neurology, Massachusetts General Hospital Boston MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thurman Wheeler
1Neurology, Massachusetts General Hospital Boston MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Citation
Genetic markers of myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) in human urine (S42.005)
Layal Antoury, Ningyan Hu, Leonora Balaj, Xandra Breakefield, Thurman Wheeler
Neurology Apr 2017, 88 (16 Supplement) S42.005;

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
0

Share

  • Article
  • Info & Disclosures
Loading

Abstract

Objective: Identify minimally invasive biomarkers of disease activity in muscular dystrophies.

Background: DM1 results from expression of a pathogenic RNA that contains an expanded CUG repeat (CUGexp) and leads to abnormal regulation of alternative pre-mRNA splicing. A previous study (Nakamori, 2013) identified DM1-specific slice outcomes in muscle biopsies as biomarkers of disease severity. Some gene deletions causing DMD are amenable to therapeutic modulation of RNA splicing to restore the open reading frame and produce a partially functional dystrophin protein. In clinical trials for DM1 and DMD, serial muscle biopsies are used to monitor therapeutic antisense oligonucleotide (ASO) drug effects on splicing outcomes. Extracellular RNA (exRNA) in serum and urine includes mRNA and non-coding RNA that can serve as genetic biomarkers of glioblastoma, prostate cancer, and other disease states.

Design/Methods: We isolated exRNA from urine and serum samples of individuals with DM1 (N=18), DMD due to deletion mutations (N=3), and unaffected (UA) controls (N=16), examined RNA integrity by capillary gel electrophoresis, gene expression by qPCR, splicing by RT-PCR, and DMD deletion transcripts by sequencing.

Results: In the urine, 11 of 30 transcripts examined show differential splicing in DM1 as compared to DMD and UA subjects, and display the characteristic pattern found muscle biopsies. By contrast, alternative splicing of these transcripts in serum is similar in DM1, DMD, and UA subjects. In DMD subjects, sequencing of urine exRNA confirms the presence of dystrophin gene deletions amenable to therapeutic exon-skipping ASOs.

Conclusions: Human urine contains genetic markers of DM1 and DMD. The surprising ability to monitor mRNA splicing outcomes in urine may reduce or eliminate the need for muscle biopsies to follow therapeutic ASO effects in DM1 and DMD.

Study Supported by: Slye family fund and NIH (NCIP01CA069246).

Disclosure: Dr. Antoury has nothing to disclose. Dr. Hu has nothing to disclose. Dr. Balaj has nothing to disclose. Dr. Breakefield has nothing to disclose. Dr. Wheeler has received (royalty or license fee or contractual rights) payments from Ionis Pharmaceuticals. Dr. Wheeler has received research support from Sanofi Innovative Awards Program.

Letters: Rapid online correspondence

No comments have been published for this article.
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
  • Info & Disclosures
Advertisement

Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study

Dr. Robert Shapiro and Dr. Amynah Pradhan

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 100 (5)

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: Education
  • 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

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise