MILD RESISTANCE TO THYROID-HORMONE WITH A TRUNCATED THYROID-HORMONE RECEPTOR-BETA

Recent studies have revealed mutations in the thyroid hormone receptor beta (TR beta) gene as a cause of the most cases of the thyroid hormo ne resistance syndrome. We have identified a novel nonsense mutation i n codon 449 in the 3' end of exon 10 in the TR beta gene in a 16-year- old male patient with generalized resistance to thyroid hormone who al so had familial thyroxine binding globulin deficiency. Receptor protei n generated from this gene is thought to be 13 amino acid deficient at carboxy-terminus. Resistance to thyroid hormone was mild at least whe n the patient was evaluated. The patient was eumetabolic in the presen ce of elevated plasma-free thyroid hormone levels, and both thyrotrope and peripheral tissues responded to triiodothyronine (T-3) administra tion. This mildness of resistance is in contrast to severe resistance to thyroid hormone in two previously reported cases with truncated rec eptors in which 16 amino acids or 11 amino acids were deficient at C-t erminus. Thus, truncation of C-terminus of thyroid hormone receptor be ta does not uniformly produce severe resistance.