Korean J Pediatr.  2007 Jun;50(6):576-579. 10.3345/kjp.2007.50.6.576.

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

• Shin JY
• Ki CS
• Kim JK

• KMID: 2278491
• DOI: http://doi.org/10.3345/kjp.2007.50.6.576

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 (TRbeta) 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.

Keyword

Resistance to thyroid hormone (RTH); Thyroid hormone receptor beta (TRbeta); Thyroid hormone receptor beta gene (THRB)

MeSH Terms

Child, Preschool
Codon
Female
Genes, erbA*
Goiter
Histidine
Humans
Parents
Reference Values
Sequence Analysis
Thyroid Gland*
Thyroid Hormone Receptors beta
Thyrotropin
Thyrotropin-Releasing Hormone
Tyrosine
Codon
Histidine
Thyroid Hormone Receptors beta
Thyrotropin
Thyrotropin-Releasing Hormone
Tyrosine