Two Novel Mutations in the Thyroid Hormone Receptor β in Patients with Resistance to Thyroid Hormone (RTH β): Clinical, Biochemical, and Molecular Data.

The syndrome of resistance to thyroid hormone (RTH β) is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,30- l -triiodothyronine (T 3 ), with persistent elevation of free-circulating T 3 (FT 3 ) and free thyroxine (FT 4 ) levels in association with nonsuppressed serum thyrotropin (TSH). Clinical presentation is variable and the molecular analysis of THRB gene provides a short cut diagnosis. Here, we describe 2 cases in which RTH β was suspected on the basis of laboratory findings. The diagnosis was confirmed by direct THRB sequencing that revealed 2 novel mutations: the heterozygous p.Ala317Ser in subject 1 and the heterozygous p.Arg438Pro in subject 2. Both mutations were shown to be deleterious by SIFT, PolyPhen, and Align GV-GD predictive methods.