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

Advertisement

Research Article Free access | 10.1172/JCI119555

Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein.

W Rottbauer, M Gautel, J Zehelein, S Labeit, W M Franz, C Fischer, B Vollrath, G Mall, R Dietz, W Kübler, and H A Katus

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Rottbauer, W. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Gautel, M. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Zehelein, J. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Labeit, S. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Franz, W. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Fischer, C. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Vollrath, B. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Mall, G. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Dietz, R. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

Find articles by Kübler, W. in: JCI | PubMed | Google Scholar

Medizinische Klinik III, Universität Heidelberg, D-69115 Heidelberg, Germany. Rattbaue@medinf.mu-luebeck.de

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

Published July 15, 1997 - More info

Published in Volume 100, Issue 2 on July 15, 1997
J Clin Invest. 1997;100(2):475–482. https://doi.org/10.1172/JCI119555.
© 1997 The American Society for Clinical Investigation
Published July 15, 1997 - Version history
View PDF
Abstract

Familial hypertrophic cardiomyopathy is a disease generally believed to be caused by mutations in sarcomeric proteins. In a family with hypertrophic cardiomyopathy linked to polymorphic markers on chromosome 11, we found a new mutation of a splice donor site of the cardiac myosin-binding protein-C gene. This mutation causes the skipping of the associated exon in mRNA from lymphocytes and myocardium. Skipping of the exon with a consecutive reading frame shift leads to premature termination of translation and is thus expected to produce a truncated cardiac myosin-binding protein-C with loss of the myosin- and titin-binding COOH terminus. However, Western blot analysis of endomyocardial biopsies from histologically affected left ventricular myocardium failed to show the expected truncated protein. These data show for the first time that a splice donor site mutation in the myosin-binding protein-C gene is transcribed to cardiac mRNA. Truncated cardiac myosin-binding protein-C does not act as a "poison polypeptide," since it seems not to be incorporated into the sarcomere in significant amounts. The absence of mutant protein and of significantly reduced amounts of wild-type protein in the presence of the mutated mRNA argues against the "poison protein" and the "null allele" hypotheses and suggests yet unknown mechanisms relevant to the genesis of chromosome-11- associated familial hypertrophic cardiomyopathy.

Version history
  • Version 1 (July 15, 1997): 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

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