title: [Point mutation of T3 receptor-beta gene and syndrome of inappropriate secretion of TSH].
abstract: Thyroid hormone receptors (TRs) are bound to the T3-responsive element of DNA as dimers and heterodimerization with TR-auxiliary protein (TRAP) strongly enhances this binding. In affected members of families with the thyroid hormone resistance syndrome, significant point mutations have been identified in the hormone-binding domain of one of the two alleles of the TR beta gene, especially in two "hot spot" regions, avoiding the regions required for DNA binding, dimerization or binding to TRAP. These findings suggested that DNA-binding and receptor dimerization are important for dominant negative inhibition by the mutant TR, which is responsible for thyroid hormone resistance in a heterozygous patient with a point mutation in the TR beta gene.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Kyushu University.
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Fujishima
mesh_terms: D004247:DNA / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology / Q000235:genetics*; D007223:Infant; D008297:Male; D017354:Point Mutation; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D004247:DNA