Familial Elevation of Serum Thyroxine-Binding Capacity

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

“…TBPA concentration was normal in our families and in others (5,8,10,11,14,15,20). In only one family (L-6) TBPA levels appeared to have an inverse correlation with the TBG capacity (13).…”

“…Hypotheses such as production of an abnormal protein with altered binding affinity and/or capacity (4, 5, 11, 12, 15, 16, 18, 20), presence of an abnormal substance interfering with TR-binding to TBG (5) or absence of normally present extraneous inhibitor of T&-protein interaction (20), abnormality in the mechanism controlling TBG synthesis and possible degradation resulting in quantitative variations in TBG concentration (5,12,15,18,20), and presence of two types of TBG controlled by different genes (5), have been considered. Based on the model of genetic control of protein synthesis in bacteria, structural gene mutations (4,5,11,16,18,20), mutations at the control sites (repressor) or operator (5,16,18), and structural gene duplication resulting in double quantity of dose of a gene (16,18) have been also considered.…”

“…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).…”

“…Because of the presence of TBG in the hemizygous-affected subjects and inability to distinguish the heterozygous state with certainty, in three out of nine families, X-linked mode of inheritance was less obvious (8,9,12). Similarly, only in four of the six families with increased T4-binding capacity of TBG was X-linked pattern of inheritance recognized (16)(17)(18)(19), whereas, in two, an autosomal dominant transmission was suggested (15,20). On closer scrutiny, it appears that except for two families with unpublished pedigrees (6,14) no instance of incompatibility with Xlinkage could be demonstrated.…”

A Family with Hereditary High Serum Thyroxine-Binding Globulln.

“…To our knowledge there have been 29 additional families with high TBG reported since then [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. It is an extremely rare disease even at present in comparison with hereditary TBG deficiency.…”