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

doi:10.1073/pnas.86.22.8977

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

Internal Medicine

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252 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 language	English
Pages (from-to)	8977-8981
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	86
Issue number	22
DOIs	https://doi.org/10.1073/pnas.86.22.8977
State	Published - 1989

Keywords

polymerase chain reaction
transcription
translation
triiodothyronine

ASJC Scopus subject areas

General

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10.1073/pnas.86.22.8977

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Sakurai, A., Takeda, K., Ain, K., Ceccarelli, P., Nakai, A., Seino, S., Bell, G. I., Refetoff, S., & DeGroot, L. J. (1989). Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β. Proceedings of the National Academy of Sciences of the United States of America, 86(22), 8977-8981. https://doi.org/10.1073/pnas.86.22.8977

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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.",

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Sakurai, A, Takeda, K, Ain, K, Ceccarelli, P, Nakai, A, Seino, S, Bell, GI, Refetoff, S & DeGroot, LJ 1989, 'Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β', Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 22, pp. 8977-8981. https://doi.org/10.1073/pnas.86.22.8977

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β. / Sakurai, A.; Takeda, K.; Ain, K. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 22, 1989, p. 8977-8981.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β

AU - Sakurai, A.

AU - Takeda, K.

AU - Ain, K.

AU - Ceccarelli, P.

AU - Nakai, A.

AU - Seino, S.

AU - Bell, G. I.

AU - Refetoff, S.

AU - DeGroot, L. J.

PY - 1989

Y1 - 1989

N2 - 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.

AB - 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.

KW - polymerase chain reaction

KW - transcription

KW - translation

KW - triiodothyronine

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

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