Inherited Heat-Stable Variant Thyroxine-Binding Globulin (TBG-Chicago)∗

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Abstract
The five known types of inherited variant T4- binding globulin (TBG) have in common increased sensitivity to heat denaturation compared to the common typeTBG (TBGC). 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-yr-old black man without personal or family history of thyroiddisease. His native TBG (nTBG) in serum had a t∗ of denaturation at 56 C of 90 mincompared to a mean value of 6.8 ± 1.1 (±S.D) 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 Xchromosome linked. The mother ofthe prppositus was heterozygous; her serum contained approximately 40/ TBG-Chicago and 60/ of another variant TBG comrnon in blacks, TBG-S. The father had TBG-C, a trait that wasnot 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.