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

April 14, 2020; 94 (15 Supplement) Wednesday, April 29

Atypical phenotypes caused by the ATP1A3 variant p.P775L (1946)

Daniel Calame, Marwan Shinawi, Julie Cohen, Richard Person, Aida Telegrafi, Timothy Lotze, Sho Yano, Debra Regier
First published April 14, 2020,
Daniel Calame
1Texas Children’s Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marwan Shinawi
2Washington University in St. Louis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie Cohen
3Kennedy Krieger Institute
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Person
4GeneDx
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aida Telegrafi
4GeneDx
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Lotze
1Texas Children’s Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sho Yano
5NIH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Debra Regier
6Children’s National Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Citation
Atypical phenotypes caused by the ATP1A3 variant p.P775L (1946)
Daniel Calame, Marwan Shinawi, Julie Cohen, Richard Person, Aida Telegrafi, Timothy Lotze, Sho Yano, Debra Regier
Neurology Apr 2020, 94 (15 Supplement) 1946;

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: To describe atypical phenotypes associated with the p.P775L variant of ATP1A3, the gene encoding the alpha subunit of the Na/K-ATPase.

Background: ATP1A3 variants cause three distinct phenotypes, namely alternating hemiplegia of childhood (AHC), rapid onset dystonia-parkinsonism (RDP) and cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS). The spectrum of ATP1A3-related disease has recently expanded to include fever-induced paroxysmal weakness and encephalopathy (FIPWE) and catastrophic early life epilepsy. While spastic diplegia has been described in AHC and RDP, it has not been reported as isolated ATP1A3-related phenotype.

Design/Methods: One patient was identified at Texas Children’s Hospital by exome sequencing through Baylor Genetics Laboratories. Three additional patients were identified by querying GeneDx’s database for patients with the variant. Variants were confirmed by Sanger sequencing. Clinical data was collected from clinicians.

Results: Two patients had only developmental delay, mild intellectual disability and spastic diplegia. One also had sickle cell disease and had progressive gait deterioration triggered by pain crises. A third patient exhibited developmental delay, mild intellectual disability, spastic diplegia, hypotonia, epilepsy, and failure to thrive. Neither dystonia nor parkinsonism were observed in these patients. A fourth patient was developmentally normal until sixteen months of age when he had a febrile illness and prolonged episode of apnea and abnormal movements. He subsequently had severe static encephalopathy, microcephaly, spastic quadriplegia, epilepsy and dystonia. Two patients had de novo ATP1A3 variants. The other two patients’ fathers were not available for testing, but their mothers did not have the variant. The affected residue is highly conserved, and the variant is predicted to be deleterious with a CADD score of 34.

Conclusions: The p.P775L ATP1A3 variant causes developmental delay, spastic diplegia, epilepsy, and episodic neurological deterioration. Thus, ATP1A3 should be considered in the differential for diplegic cerebral palsy. These phenotypes are distinct from AHC and RDP.

Disclosure: Dr. Calame has nothing to disclose. Dr. Shinawi has nothing to disclose. Dr. Cohen has nothing to disclose. Dr. Person has nothing to disclose. Dr. Telegrafi has nothing to disclose. Dr. Lotze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with He has served as a consultant/speaker for Biogen.. Dr. Lotze has received research support from PTC Therapeutics, Serepta Therapeutics and Catalyst Therapeutics. Dr. Yano has nothing to disclose. Dr. Regier has nothing to disclose.

Disputes & Debates: Rapid online correspondence

No comments have been published for this article.
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 the last 8 weeks.
  • 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
  • Info & Disclosures
Advertisement

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 96 (9)

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