Coexistence of THRB and TBG gene mutations in a Turkish family.

Objective: Resistance to thyroid hormone is a syndrome characterized by high serum free T4 levels and unsuppressed serum TSH concentration. Thyroxine-binding globulin complete deficiency manifests with low serum total T4 and T3 levels and normal serum TSH concentration. Our objective is to describe a family with the coexistence of resistance to thyroid hormone and thyroxine-binding globulin complete deficiency.

Methods: We conducted clinical studies and genetic analyses.

Results: The proband presented with mental retardation, hearing loss, and recurrent upper respiratory tract infections accompanied by high serum levels of TSH, T3, T4, and high thyroglobulin antibody titers. His elder sister presented with normal TSH and T3 and high serum T4 levels. Both patients were found to be heterozygous for the mutation P453A in the thyroid hormone receptor beta (THRB) gene. One of the proband's brothers had low serum total T3 and T4 and normal TSH concentrations, without any clinical manifestations. He was hemizygous for the mutation P50fs51X in the TBG gene. The proband's mother showed slightly elevated TSH, normal total T3 and T4, and elevated titers of thyroperoxidase antibodies and thyroglobulin antibodies. She was heterozygous for both THRB and TBG genes mutations.

Conclusions: To our knowledge, this is the first report of the coexistence of THRB and TBG gene mutations in the same individual (mother of the proband), whereas other affected family members had only 1 of the 2 genes mutated. The case illustrates the difficulty that might be encountered in the interpretation of thyroid function tests when different genetic defects affecting thyroid function coexist.