Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β

A. Sakurai, K. Takeda, K. Ain, P. Ceccarelli, A. Nakai, S. Seino, G. I. Bell, S. Refetoff, L. J. DeGroot

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine → cytosine replacement in the codon for amino acid 340 resulted in a glycine → arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

Original languageEnglish
Pages (from-to)8977-8981
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number22
DOIs
StatePublished - 1989

Keywords

  • polymerase chain reaction
  • transcription
  • translation
  • triiodothyronine

ASJC Scopus subject areas

  • General

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