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| Author(s): |
Paola Rossi Mezalira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2011-03-10 |
| Examining board members: |
Geraldo Antonio de Medeiros Neto;
Janete Maria Cerutti;
Chin Jia Lin
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| Advisor: | Geraldo Antonio de Medeiros Neto |
| Abstract | |
Introduction: Congenital hypothyroidism is the most common cause of preventable mental retardation in children, its incidence varies from 1:2000 to 1:3000 live births. It is estimated that 15-20% of cases of CH are consistent failures in the synthesis of thyroid hormones. Among the most frequent genetic changes highlight the defect in the activity of thyroid peroxidase. Objectives: Identify mutations in two patients with CH and partial defect in iodide incorporation and verify the functional effect of changes in gene tireperoxidase. Methods: Two patients with CH, goiter and molecular diagnosis unknown. Samples of peripheral blood and thyroid tissue of patients and DNA samples from control subjects. Sequencing of the TPO gene, DUOX2 and DUOXA2. Analysis of gene expression of TPO, TG, NKX2.1, PDS, PAX8, NIS and TSHr by real time. Evaluation of the expression of luciferase under control of the promoter of TPO and TPO activity evaluation of the patients tissue. Results: The patients were identified change-95G> T homozygous, in the promoter region of TPO. We observed decrease in enzymatic activity of TPO in thyroid tissues of patients and decreased RNAm expression of this gene. Also found decreased expression of genes NKX2.1 and PAX8. Since the genes TG, TSHr, PDS, NIS mRNA expression presented increased. Functional analysis of the change -95G>T showed no descrease in reporter gene expression. Conclusion: The CH of patients due to decreased enzymatic activity of TPO, but changes were not found in the sequence of TPO gene to explain the decrease in activity. Epigenetic alterations in introns or in the TPO gene could explain the HC patients (AU) | |