A Novel Point Mutation (R243Q) in Exon 7 of the c-erbAβ Thyroid Hormone Receptor Gene in a Family with Resistance to Thyroid Hormone

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormones. Recently, a large number of different point mutations have been identified in the c-erbAβ thyroid hormone receptor (TRβ) in subjects with RTH. We describe a Japanese family with RTH with a novel point mutation in exon 7 of the TRβ gene. A single nucleotide substitution, guanine for adenine, was identified at the second position of codon 243 located in the hinge domain between the ligand binding and DNA binding domains in one of the two alleles of the proband and his mother, resulting in the substitution of the normal arginine (CGG) with a glutamine (CAG). Except for one family, point mutations so far described in RTH are clustered at exons 8–10 of the TRβ gene. This report presents a novel mutation in the characteristic portion in exon 7 of the TRβ.