Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article (56)

Advertisement

Research Article Free access | 10.1172/JCI116455

Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect.

H Morisaki, T Morisaki, L K Newby, and E W Holmes

Seymour Gray Molecular Medicine Laboratory, Department of Medicine, University of Pennsylvania, Philadelphia 19104-4283.

Find articles by Morisaki, H. in: PubMed | Google Scholar

Seymour Gray Molecular Medicine Laboratory, Department of Medicine, University of Pennsylvania, Philadelphia 19104-4283.

Find articles by Morisaki, T. in: PubMed | Google Scholar

Seymour Gray Molecular Medicine Laboratory, Department of Medicine, University of Pennsylvania, Philadelphia 19104-4283.

Find articles by Newby, L. in: PubMed | Google Scholar

Seymour Gray Molecular Medicine Laboratory, Department of Medicine, University of Pennsylvania, Philadelphia 19104-4283.

Find articles by Holmes, E. in: PubMed | Google Scholar

Published May 1, 1993 - More info

Published in Volume 91, Issue 5 on May 1, 1993
J Clin Invest. 1993;91(5):2275–2280. https://doi.org/10.1172/JCI116455.
© 1993 The American Society for Clinical Investigation
Published May 1, 1993 - Version history
View PDF
Abstract

Approximately 2% of Caucasians and African-Americans are homozygous for a nonsense mutation in exon 2 of the AMPD1 (AMP deaminase) gene. These individuals have a high grade deficiency of AMPD activity in their skeletal muscle. More than 100 patients with AMPD1 deficiency have been reported to have symptoms of a metabolic myopathy, but it is apparent many individuals with this inherited defect are asymptomatic given the prevalence of this mutant. Results of the present study provide a potential molecular explanation for "correction" of this genetic defect. Alternative splicing eliminates exon 2 in 0.6-2% of AMPD1 mRNA transcripts in adult skeletal muscle. Expression studies document that AMPD1 mRNA, which has exon 2 deleted, encodes a functional AMPD peptide. A much higher percentage of alternatively spliced transcripts are found during differentiation of human myocytes in vitro. Transfection studies with human minigene constructs demonstrate that alternative splicing of the primary transcript of human AMPD1 is controlled by tissue-specific and stage-specific signals. Alternative splicing of exon 2 in individuals who have inherited this defect provides a mechanism for phenotypic rescue and variations in splicing patterns may contribute to the variability in clinical symptoms.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 2275
page 2275
icon of scanned page 2276
page 2276
icon of scanned page 2277
page 2277
icon of scanned page 2278
page 2278
icon of scanned page 2279
page 2279
icon of scanned page 2280
page 2280
Version history
  • Version 1 (May 1, 1993): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article (56)

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts