All issues > Volume 50(6); 2007

Case Report

Korean J Pediatr. 2007;50(6):576-579. Published online June 15, 2007.

Identification of a de novo mutation (H435Y) in the THRB gene in a Korean patient with resistance to thyroid hormone

Jin Young JY Shin¹, Chang-Seok CS Ki², Jin Kyung JK Kim¹

¹Department of Pediatrics, Catholic University of Daegu School of Medicine, Korea
²Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine

Correspondence Jin Kyung JK Kim ,Email: kimjk@cu.ac.kr

Abstract

The syndrome of resistance to thyroid hormone (RTH) is characterized by reduced tissue sensitivity to thyroid hormone (TH). In the majority of subjects, RTH is caused by mutations in the thyroid hormone receptor beta (TRβ) gene, located on the chromosome locus 3p24.3. RTH is inherited in an autosomal dominant manner. The clinical presentation of RTH is variable, but common features include elevated serum levels of thyroid hormone (TH), a normal or slightly increased thyrotropin (thyroid stimulating hormone, TSH) level that responds to thyrotropin releasing hormone (TRH), and goiter. We report a 4 year-old girl, who was clinically euthyroid in spite of high total and free T4, and T3 concentrations, while TSH was slightly increased. Sequence analysis of the thyroid hormone receptor beta gene (THRB) confirmed a heterozygous C to T change at nucleotide number 1303, resulting in a substitution of histidine by tyrosine at codon 435 (H435Y). Further analysis of her parents revealed that the H435Y variation was a de novo mutation since neither parents had the variation. Her parents' TH and TSH levels were within normal range.

Keywords :Resistance to thyroid hormone (RTH), Thyroid hormone receptor beta (TRβ), Thyroid hormone receptor beta gene (THRB)