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
UR - https://www.scopus.com/pages/publications/0024370742
UR - https://www.scopus.com/pages/publications/0024370742#tab=citedBy
U2 - 10.1073/pnas.86.22.8977
DO - 10.1073/pnas.86.22.8977
M3 - Article
C2 - 2510172
AN - SCOPUS:0024370742
SN - 0027-8424
VL - 86
SP - 8977
EP - 8981
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -