A Novel Thyroid Hormone Receptor-Beta Mutation, Not Anticipated to Occur in Resistance to Thyroid Hormone, Causes Variable Phenotypes
| Autor: | H. Trouette, Antoine Tabarin, M. Monsaingeon, A. Margotat, B. Catargi, N. Ronci-Chaix, V. Bex-Bachellerie, Paolo Beck-Peccoz |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Thyroid Hormones endocrine system medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism Biology medicine.disease_cause Thyroglobulin White People Thyroid hormone receptor beta Exon Endocrinology Bone Density Reference Values Thyroid peroxidase Sex Hormone-Binding Globulin Internal medicine medicine Humans Point Mutation Creatine Kinase Mutation Receptors Thyroid Hormone Thyroid hormone receptor Thyroid Thyroid Hormone Receptors beta Exons Alkaline Phosphatase Thyroid disorder Pedigree Hydroxyproline Cholesterol Phenotype medicine.anatomical_structure Amino Acid Substitution Ferritins Pediatrics Perinatology and Child Health biology.protein Triiodothyronine Female Hormone |
| Zdroj: | Hormone Research in Paediatrics. 57:137-142 |
| ISSN: | 1663-2826 1663-2818 |
| DOI: | 10.1159/000057965 |
| Popis: | Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-β (TRβ) gene. We report here for the first time in vivo the mutation R429W (CCG→TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T3-binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the propositus and his grandmother had an authentic hyperthyroidism with high FT4 plasma level in the presence of inappropriate TSH. On the other hand, spontaneous variations of clinical features and – interestingly – of plasma FT4 concentrations with time in the propositus, and the phenotype observed in his mother who never complained with thyrotoxic symptoms, confirmed the in vitro binding and functional predictions. The most intriguing is the clinical course of the grandmother as she first presented with predominant pituitary RTH and a diffuse goiter and finally with a toxic multinodular goiter with normal T3 and T4 plasma concentrations and suppressed TSH. In conclusion, we report a novel mutation in the gene encoding the thyroid hormone receptor responsible for predominant pituitary RTH already described in vitro but not in vivo. The fluctuant phenotype of the propositus suggests that other factors modulate the degree of tissue resistance that is under genetic control. Toxic multinodular goiter, possibly due to chronic TSH stimulation during RTH, in addition to the phenotype variability, increases the difficulty to diagnose this thyroid disorder. |
| Databáze: | OpenAIRE |
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