A Novel Mutation of the THRB Gene in a Japanese Family with Resistance to Thyroid Hormone.

Resistance to thyroid hormone (RTH; OMIM 190160) is an inherited syndrome of reduced sensitivity to thyroid hormone. RTH, in majority, is caused by monoallelic inactivating mutation of THRB, which encodes the thyroid hormone receptor β (TRβ) (1). RTH is endocrinologically characterized by high serum thyroid hormones together with inappropriately normal TSH. The severity of hormonal resistance varies among different tissues in an affected individual, due to differences in the relative expression of TRβ and thyroid hormone receptor alpha (TRα) in different tissues (2). To date, more than 100 THRB mutations have been reported among RTH patients. Most mutations are located in the ligand-binding domain of TR. They interfere with the function of the normal TR because of their dominant negative effect (1). We report a novel mutation of the THRB gene in a family with RTH.