Inherited heat-stable variant thyroxine-binding globulin (TBG-Chicago).
The five known types of inherited variant T4-binding globulin (TBG) have in common increased sensitivity to heat denaturation compared to the common type TBG (TBG-C). In the course of studies to screen for and characterize variant TBGs in population groups, we detected a unique TBG with marked resistance to heat denaturation. The propositus was a 22-year-old black man without personal or family history of thyroid disease. His native TBG (nTBG) in serum had a t1/2 of denaturation at 56 C of 90 min compared to a mean value of 6.8 +/- 1.1 (+/- SD) min for TBG-C. This variant TBG, termed TBG-Chicago, was also resistant to acid denaturation, but was indistinguishable from TBG-C in terms of immunoreactivity, microheterogeneity on isoelectric focusing, and affinity for T4. It had a single T4-binding site and a normal concentration in serum associated with iodothyronine levels within the normal range. The mode of inheritance of TBG-Chicago appears to be X-chromosome linked. The mother of the propositus was heterozygous; her serum contained approximately 40% TBG-Chicago and 60% of another variant TBG common in blacks, TBG-S. The father had TBG-C, a trait that was not transmitted to his son. The exact nature of this variant TBG is not known. It most likely represents a mutation in the polypeptide chain of the molecule with formation of stronger intramolecular bonds.
D000328:Adult; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D011489:Protein Denaturation; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000235:genetics*; D014960:X Chromosome
D013975:Thyroxine-Binding Proteins; C050338:thyroxine-binding globulin Chicago; D013972:Thyrotropin