Inherited Thyroxine-Binding Globulin Abnormalities in Man*

Publisher Website
Google Scholar
Abstract
Introduction and Historic Background IN 1959, Beierwaltes and Robbins (1) reported a family with T4-binding globulin (TBG) excess thus recognizing for the first time the existence of inherited TBG abnormalities in man. Subsequently, the occurrence of inherited complete (2–4) and partial (5–7) TBG deficiencies were described. These three forms of TBG abnormalities (complete deficiency, partial deficiency, and excess) followed, in general, an X-chromosome-linked inheritance pattern (7–9). Because earlier studies of these subjects failed to show physical or chemical changes of their TBG (7, 10), nor circulating substances interfering with hormone binding to the molecule (4, 11), and because labeled normal TBG tracer had normal survival time when given to the affected subjects (12), it was postulated that inherited TBG defects represent either mutations of a gene controlling TBG synthesis (12) or mutations at the promoter site of the TBG gene proper (13). In the 1980s, two new inherited TBG types were described, both involving distinct ethnic groups. In 1980/1981, Dick and Watson (14, 15) reported that the low serum total T4 (TT4) concentration found in approximately 40% of Australian Aborigines was due to a TBG variant with low affinity for T4. In 1981, Daiger et al. (16, 17) reported a TBG with slow electrophoretic mobility and with isoelectric focusing (IEF) pattern exhibiting a cathodal shift in 5–16% of subjects from African and Oceanian origin. Inheritance of these two variant TBGs was shown also to be X-chromosome-linked (16, 18), suggesting that the structural gene of the molecule is located on the X-chromosome. Over the past 3 yr, five additional TBG variants were detected (19–22). Four were associated with partial TBG deficiency (19–21), and three of these were found to have high serum levels of denatured TBG (19, 20), which was measured using an antibody directed against the primary structure of the molecule. Another TBG variant had, as a sole abnormality, resistance to denaturation at high temperatures and in acid conditions (22).

This publication has 0 references indexed in Scilit: