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

Abstract

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.

Thyroid hormone resistance syndrome with P453T mutation in thyroid hormone receptor β gene

“…[ 1 ] Mutations in the thyroid hormone receptor β (THRβ) gene are responsible for 80% to 90% of THRS cases. [ 2 ] Here, we describe a case of THRS that was suspected based on thyroid function findings. The diagnosis was confirmed by sequence analysis of the THRβ gene, which showed a heterozygous missense mutation C>A located at exon 10.…”