X-Chromosome Linked Familial Decrease in Thyroxine-Binding Globulin Activity

Study of Four New Kindreds with Inherited Thyroxine-Binding Globulin Abnormalities POSSIBLE MUTATIONS OF A SINGLE GENE LOCUS

“…TBG was also quantitated by two electrophoretic methods, a method utilizing resin as competitor of TR-binding and by radioimmunoassay giving similar results for all patients covering the spectrum of TBG abnormalities.°TBGs in both hemizygous and heterozygous members of families with low or high TBG, as well as heterozygotes from the family with TBG deficiency, have similar affinity for either To or Ts and do not differ in their behavior to heat inactivation. Other authors have shown no differences in the electrophoretic mobility on polyacrylamide (3,11,12), cellulose acetate (7), and 2 dimension paper-starch (20) electrophoreses using a variety of buffer systems. Similarity in the shape of the TBG stabilization curve of normal sera and sera from patients with inherited TBG elevation has been demonstrated (15 ing with Tt-binding to TBG.…”

“…In only one family (L-6) TBPA levels appeared to have an inverse correlation with the TBG capacity (13). Similarly, other serum proteins including CBG (3,8,16,18) 6.7 7.1 TIME (min ) FIGURE 11 Rate of TBG inactivation at 60'C. Portions of serum from each subject were heated in a constant temperature bath, for variable periods of time, as indicated on the abscissa.…”

“…globin (3,14), iron-binding globulin (3,8), and ceruloplasmin (3) were present in normal concentrations. The turnover rate of serum albumin was normal in one of our patients with TBG deficiency (5).…”

“…CBG responds normally to the administration of estrogens or to pregnancy (3,5,16). Although associated abnormalities such as hypothyroidism (3,11), toxic nodular goiter (18) (11) have been described, these associations are believed to be fortuitous. On the other hand, Shane, Seal, and…”

“…Subsequently, TBG abnormalities have been reported in 20 additional and apparently unrelated families: 15 with diminished (2-14) and 5 with excess (15)(16)(17)(18)(19) maximal capacity of thyroxine (T4) -binding to TBG. In 6 of the 15 families with diminished TBG capacity, males had no demonstrable Tt-binding to the TBG zone on electrophoresis, and with only a single exception (7), affected females had approximately half normal binding capacity (2)(3)(4)(5)7). The ability to identify the heterozygous ("carrier") state has helped establish X-chromosome-linked inheritance patterns in these families.…”