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 (64)

Advertisement

Research Article Free access | 10.1172/JCI114938

A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia.

A C Moses, H N Rosen, D E Moller, S Tsuzaki, J E Haddow, J Lawlor, J J Liepnieks, W C Nichols, and M D Benson

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

Find articles by Moses, A. in: JCI | PubMed | Google Scholar

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

Find articles by Moller, D. in: JCI | PubMed | Google Scholar

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Diabetes Unit, Charles A. Dana Research Institute, Boston, Massachusetts.

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

Published December 1, 1990 - More info

Published in Volume 86, Issue 6 on December 1, 1990
J Clin Invest. 1990;86(6):2025–2033. https://doi.org/10.1172/JCI114938.
© 1990 The American Society for Clinical Investigation
Published December 1, 1990 - Version history
View PDF
Abstract

In a family expressing euthyroid hyperthyroxinemia, an increased association of plasma thyroxine (T4) with transthyretin (TTR) is transmitted by autosomal dominant inheritance and is secondary to a mutant TTR molecule with increased affinity for T4. Eight individuals spanning three generations exhibited the abnormality. Although five of eight individuals had elevated total T4 concentrations, all affected individuals were clinically euthyroid and all had normal free T4 levels. Purified TTR from the propositus had an affinity for 125I-T4 three times that of control TTR. Exons 2, 3, and 4 (representing greater than 97% of the coding sequence) of the TTR gene of DNA prepared from the propositus' peripheral blood leukocytes were amplified using the polymerase chain reaction (PCR) and were sequenced after subcloning. Exons 2 and 3 were indistinguishable from normal. In 50% of clones amplified from exon 4, a substitution of adenine (ACC) for guanine (GCC) in codon 109 resulted in the replacement of threonine-for-alanine, a mutation confirmed by amino acid sequencing of tryptic peptides derived from purified plasma TTR. The adenine-for-guanine substitution abolishes one of two Fnu 4H I restriction sites in exon 4. PCR amplification of exon 4 of TTR and restriction digestion with Fnu 4H I confirmed that five affected family members with increased binding of 125I-T4 to TTR are heterozygous for the threonine 109 substitution that increases the affinity of this abnormal TTR for T4.

Images.

Browse pages

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

icon of scanned page 2025
page 2025
icon of scanned page 2026
page 2026
icon of scanned page 2027
page 2027
icon of scanned page 2028
page 2028
icon of scanned page 2029
page 2029
icon of scanned page 2030
page 2030
icon of scanned page 2031
page 2031
icon of scanned page 2032
page 2032
icon of scanned page 2033
page 2033
Version history
  • Version 1 (December 1, 1990): 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 (64)

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