title: Thyroid hormone receptor mutations and disease: beyond thyroid hormone resistance.
abstract: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate the biological activities of thyroid hormone (T3). Two THR genes (A and B), located on different chromosomes, yield four T3-binding isoforms with highly conserved sequences in the DNA- and ligand-binding domains. Mutations of THRB cause a human genetic disease, thyroid hormone resistance syndrome (RTH). Comprehensive genomic profiling unveiled the contribution of novel change-of-function mutations of TRbeta to the pathogenesis of RTH. In addition, abnormalities associated with mutations of the THRA gene have been uncovered recently. The phenotypic manifestations of mutated THRB and THRA genes are distinct, indicating isoform-dependent actions of TR mutants in vivo. Therefore, mutant TRs provide a new paradigm to understand the molecular basis of receptor disease.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA. sycheng@helix.nih.gov
authors.forename: Sheue-yann
authors.initials: SY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004392:Dwarfism / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D013959:Thyroid Diseases / Q000235:genetics* / Q000503:physiopathology; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000502:physiology; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000502:physiology; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics* / Q000503:physiopathology
chemical_list: D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta