INVESTIGADORES
TARGOVNIK Hector Manuel
congresos y reuniones científicas
Título:
p.P438H thyroid hormona receptor beta gene mutation responsible for hormone resistance syndrome: case report.
Autor/es:
CHAMOUX, A.; VALERIE, C.; BRE, M.; OLCESE, MARÍA CECILIA; TARGOVNIK , HÉCTOR MANUEL; RIVOLTA, CARINA MARCELA; CHIESA, ANA; BRUNETTO, O.
Lugar:
Costa do Sauipe
Reunión:
Congreso; XXI Annual Meeting of the Latin-American Society for Paediatric Endocrinology (SLEP).; 2010
Institución organizadora:
Latin-American Society for Paediatric Endocrinology (SLEP)
Resumen:
The Thyroid Hormone Resistance Syndrome (RTH), is characterized by a reduced responsiveness on target tissues to the action of thyroid hormone and is associated with mutations in the T3 binding domain of the thyroid hormone receptor gene (THRB). This genetic disorder with a dominant mode of transmission results in hormone-binding impairment which leads to a reduction in the affinity of the receptor for triiodothyronine (T3). Biochemically, RTH is defined by elevated levels of thyroid hormones with a measurable TSH in serum. The clinical manifestations may vary, but the majority of patients are euthyroid. Case Report: A 5 years old girl presented with tachycardia, palpitations, tremor, irritability, fatigue, heat intolerance, attention deficit, hyperactivity and weight loss. Laboratory analysis showed elevated serum levels of free T4, total T4, total T3 and a normal TSH value. All thyroid antibodies (Atpo, atg and Trab) were negative. Ultrasound showed a homogeneous increase of thyroid gland’s volume. We thought about RTH as presumptive diagnosis. Results: Genomic DNA was isolated from blood cells and the exons 7, 8, 9 and 10 of the THRB gene including the flanking intronic regions were amplified by PCR. DNA sequences from each amplified fragment were analysed by SSCP and sequencing. A mutation in exon 10 was identified in the patient and her mother. A c.1313G>A transition results in the replacement of arginine at codon 438 by histidine (R438H). Conclusion: Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH and may help to avoid potential misdiagnosis and inappropriate treatment.  
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