| Grant number: | 13/04210-0 |
| Support Opportunities: | Regular Research Grants |
| Start date: | July 01, 2013 |
| End date: | June 30, 2015 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Léa Maria Zanini Maciel |
| Grantee: | Léa Maria Zanini Maciel |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Associated researchers: | Maria Izabel Chiamolera |
Abstract
Resistance Syndrome Thyroid Hormone (RTH) is a rare disease, described in 1967 by Refetoff, DeWind and DeGroot, in two siblings of a consanguineous family who had clinical manifestations suggestive of hypothyroidism, however, laboratory tests indicated excess of thyroid hormones (TH). Since 1967 over 3000 individuals with RTH, in over 1000 families have been identified, resulting in the description of more than 170 mutations in the thyroid hormone receptor (TR). The RTH is characterized biochemically by elevated concentrations of TH and not suppressed TSH. The main clinical data are goiter and tachycardia. In 85% of cases relates to mutations in the TR² gene. In almost all subjects, inheritance is autosomal dominant. The TR mutant may have lower affinity for T3 and / or abnormal interaction with complex coactivators (CoA) and corepressors (CoR) needed to perform their actions, or even actions of TRs interference with normal TRs, a phenomenon named dominant negative effectAt Division of Endocrinology, in the Hospital of the School of Medicine of Ribeirão Preto, University of São Paulo (USP-HCFMRP) were diagnosed and studied 16 individuals with RTH, from eight families. Six mutations were found in regions hot spots of the exons 9 and 10 of the ligand binding domain (LBD) of TR², two of which are unprecedented in the literature.The objective of this project is to validate the new mutations found by functional study of the mutants receptors. (AU)
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