title: Coexistence of THRB and TBG gene mutations in a Turkish family.
abstract: 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.
authors: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors: Alfonso Massimiliano
authors: AM
authors: Ferrara
authors: Mehtap
authors: M
authors: Cakir
authors: Phillip H
authors: PH
authors: Henry
authors: Samuel
authors: S
authors: Refetoff
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013960:Thyroid Function Tests; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D056825:Thyroxine-Binding Globulin / Q000235:genetics*; D014421:Turkey
chemical_list: D037042:Thyroid Hormone Receptors beta; D056825:Thyroxine-Binding Globulin
references: Thyroid. 1994 Fall;4(3):249-54
references: 7833659
references: Mol Endocrinol. 1994 Sep;8(9):1262-77
references: 7838159
references: J Clin Endocrinol Metab. 1999 Feb;84(2):401-4
references: 10022391
references: J Clin Endocrinol Metab. 2012 Apr;97(4):1328-36
references: 22319036
references: J Pediatr. 2003 Sep;143(3):296-301
references: 14517508
references: J Endocrinol Invest. 2005 Apr;28(4):379-83
references: 15966514
references: Intern Med J. 2006 Nov;36(11):738-41
references: 17040361
references: Endocr Rev. 1989 Aug;10(3):275-93
references: 2506004
references: J Mol Med (Berl). 2006 Oct;84(10):864-71
references: 16947003
references: Exp Clin Endocrinol Diabetes. 2009 Jan;117(1):34-7
references: 18561095
references: Endocr Rev. 1993 Jun;14(3):348-99
references: 8319599
references: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 Aug;23(4):423-6
references: 16883531
references: J Clin Invest. 1994 Aug;94(2):506-15
references: 8040303
references: Ann Endocrinol (Paris). 2001 Jun;62(3):220-5
references: 11458173