Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • 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
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • 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
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit 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 14, 2020; 94 (15 Supplement) Thursday, April 30

Family-Based Genome Analysis Identifies Clinically Relevant de novo Variants in Pediatric Dystonia (4446)

Bahareh Adhamimojarad, Yue Yin, Ian Backstrom, Ryan Yuen, Teesta Soman
First published April 14, 2020,
Bahareh Adhamimojarad
1Genetics and genome biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yue Yin
3The hospital for sick children
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian Backstrom
1Genetics and genome biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan Yuen
1Genetics and genome biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Teesta Soman
2Neurology, The hospital for sick children
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Citation
Family-Based Genome Analysis Identifies Clinically Relevant de novo Variants in Pediatric Dystonia (4446)
Bahareh Adhamimojarad, Yue Yin, Ian Backstrom, Ryan Yuen, Teesta Soman
Neurology Apr 2020, 94 (15 Supplement) 4446;

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: Application of advanced genomic technologies capturing a greater variety of genetic variants identifies known and novel inherited/de novo variants contributing to dystonia etiology in parent-child trios with no genetic diagnosis using routine clinical genetic tests.

Background: Dystonia is a movement disorder characterized by sustained/intermittent muscle contractions. It can be genetically inherited, acquired from brain injury, or arise spontaneously in individuals with no family history of the disorder. To date, variants in ~15 genes are implicated in different forms of dystonia, designated as DYT loci, the majority of which follow autosomal dominant inheritance. Clinical and genetic heterogeneity of dystonia challenges the identification of its underlying genetic risk, and hence genetic diagnosis.

Design/Methods: We performed whole genome sequencing (WGS) on nine families with dystonia (8 families) and dyskinesia (one family) with no genetic causes found from prior genetic tests. We sequenced the affected individuals, their parents, and siblings (n=30). We assessed rare genetic variants, including single nucleotide variants, small insertions and deletions, copy number and structural variants for potential clinical relevance based on their predicted damage to genes implicated in dystonia/related disorders.

Results: A de novo pathogenic loss-of-function (LoF) frameshift insertion in PRRT2 was identified in an affected individual with paroxysmal kinesigenic dyskinesia and epilepsy. LoF variants in PRRT2 are reported in individuals with dystonia/paroxysmal kinesigenic dyskinesia. We also identified a de novo frameshift deletion in TCEAL5 on the X chromosome of a male individual with generalized dystonia, choreoathetosis and global developmental delay. TCEAL5 is highly expressed in brain with no known function. Four other de novo missense variants of uncertain significance from 3 families were present in SEC16A, BUD23, LAMA5 and STAB2, awaiting further research determining their relevance.

Conclusions: We demonstrate the power of family-based WGS to uncover the contributions of genetic variants to dystonia/dyskinesia liability that were undetected using routine clinical gene panel testing.

Disclosure: Dr. Adhamimojarad has nothing to disclose. Dr. Yin has nothing to disclose. Dr. Backstrom has nothing to disclose. Dr. Yuen has nothing to disclose. Dr. Soman has nothing to disclose.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

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

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease–Related Dementias

Dr. Sevil Yaşar and Dr. Behnam Sabayan

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 101 (13)

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