title: Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.
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 beta gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor beta gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.
authors.affiliation: Thyroid Study Unit, University of Chicago, IL 60637.
authors.forename: A
authors.initials: A
authors.lastname: Sakurai
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Ain
authors.forename: P
authors.initials: P
authors.lastname: Ceccarelli
authors.forename: A
authors.initials: A
authors.lastname: Nakai
authors.forename: S
authors.initials: S
authors.lastname: Seino
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: S
authors.initials: S
authors.lastname: Refetoff
authors.forename: L J
authors.initials: LJ
authors.lastname: DeGroot
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D002648:Child; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D007438:Introns; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D013959:Thyroid Diseases / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000032:analysis; D014284:Triiodothyronine / Q000097:blood / Q000627:therapeutic use*
chemical_list: D008024:Ligands; D011988:Receptors, Thyroid Hormone; D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine