title: Mild resistance to thyroid hormone with a truncated thyroid hormone receptor beta.
abstract: Recent studies have revealed mutations in the thyroid hormone receptor beta (TR beta) gene as a cause of the most cases of the thyroid hormone resistance syndrome. We have identified a novel nonsense mutation in codon 449 in the 3' end of exon 10 in the TR beta gene in a 16-year-old male patient with generalized resistance to thyroid hormone who also had familial thyroxine binding globulin deficiency. Receptor protein generated from this gene is thought to be 13 amino acid deficient at carboxy-terminus. Resistance to thyroid hormone was mild at least when the patient was evaluated. The patient was eumetabolic in the presence of elevated plasma-free thyroid hormone levels, and both thyrotrope and peripheral tissues responded to triiodothyronine (T3) administration. This mildness of resistance is in contrast to severe resistance to thyroid hormone in two previously reported cases with truncated receptors in which 16 amino acids or 11 amino acids were deficient at C-terminus. Thus, truncation of C-terminus of thyroid hormone receptor beta does not uniformly produce sever resistance.
authors.affiliation: Third Dept. of Internal Medicine, School of Medicine, Showa University (Tokyo), Japan.
authors.forename: M
authors.initials: M
authors.lastname: Taniyama
authors.forename: S
authors.initials: S
authors.lastname: Kusano
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Kaihara
authors.forename: T
authors.initials: T
authors.lastname: Tobe
authors.forename: M
authors.initials: M
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Katagiri
authors.forename: Y
authors.initials: Y
authors.lastname: Ban
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013972:Thyrotropin / Q000097:blood / Q000187:drug effects; D013974:Thyroxine / Q000097:blood / Q000187:drug effects; D014284:Triiodothyronine / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D004247:DNA; D013974:Thyroxine