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/JCI117172

A novel exon in the cystic fibrosis transmembrane conductance regulator gene activated by the nonsense mutation E92X in airway epithelial cells of patients with cystic fibrosis.

K Will, T Dörk, M Stuhrmann, T Meitinger, R Bertele-Harms, B Tümmler, and J Schmidtke

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

Find articles by Will, K. in: PubMed | Google Scholar

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

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

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

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

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

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

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

Find articles by Bertele-Harms, R. in: PubMed | Google Scholar

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

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

Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

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

Published April 1, 1994 - More info

Published in Volume 93, Issue 4 on April 1, 1994
J Clin Invest. 1994;93(4):1852–1859. https://doi.org/10.1172/JCI117172.
© 1994 The American Society for Clinical Investigation
Published April 1, 1994 - Version history
View PDF
Abstract

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report on a novel nonsense mutation that leads to exon skipping and the activation of a cryptic exon. Screening of genomic DNA from 700 German patients with CF uncovered four cases with the nonsense mutation E92X, a G-->T transversion that creates a termination codon and affects the first base of exon 4 of the CFTR gene. Lymphocyte RNA of two CF patients heterozygous for E92X was found to contain the wild type sequence and a differentially spliced isoform lacking exon 4. In RNA derived from nasal epithelial cells of E92X patients, a third fragment of longer size was observed. Sequencing revealed the presence of E92X and an additional 183-bp fragment, inserted between exons 3 and 4. The 183-bp sequence was mapped to intron 3 of the CFTR gene. It is flanked by acceptor and donor splice sites. We conclude that the 183-bp fragment in intron 3 is a cryptic CFTR exon that can be activated in epithelial cells by the presence of the E92X mutation. E92X abolishes correctly spliced CFTR mRNA and leads to severe cystic fibrosis.

Images.

Browse pages

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

icon of scanned page 1852
page 1852
icon of scanned page 1853
page 1853
icon of scanned page 1854
page 1854
icon of scanned page 1855
page 1855
icon of scanned page 1856
page 1856
icon of scanned page 1857
page 1857
icon of scanned page 1858
page 1858
icon of scanned page 1859
page 1859
Version history
  • Version 1 (April 1, 1994): 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