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. 1987 Mar;79(3):833–840. doi: 10.1172/JCI112891

Two new inherited defects of the thyroxine-binding globulin (TBG) molecule presenting as partial TBG deficiency.

J Takamatsu, S Refetoff, M Charbonneau, J H Dussault
PMCID: PMC424213  PMID: 3102557

Abstract

Serum-denatured TBG (dnTBG) measured in 32 families deficient in native TBG (nTBG) was undetectable in all subjects with complete nTBG deficiency and was high in 2 of 16 families with partial nTBG deficiency. nTBG (in mean micrograms per decaliter +/- SD) in members of the Quebec and Montreal families, respectively were: 258 +/- 54 and 230 in affected men, 747 +/- 190 and 927 +/- 90 in affected women, and 1568 +/- 151 and 1300 +/- 195 in unaffected relatives. Corresponding mean dnTBG levels were: 14.3 +/- 2.9 and 21.3 in affected men, 8.6 +/- 1.0 and 11.6 +/- 3.1 in affected women, and less than 2.1 and less than 2.6 in unaffected relatives. All were euthyroid with normal free thyroxine and thyrotropin levels. In comparison to common type TBG, TBG-Quebec was more heat labile by 10 degrees C and TBG-Montreal by 12 degrees C. The degree of dnTBG elevation and nTBG lability at 37 degrees C were correlated (r = 0.99). Isoelectric focusing showed cathodal shift of all TBG bands: TBG-Quebec by 0.06 isoelectric points (pI) and TBG-Montreal by 0.02 pI. These two TBG variants represent different mutations most likely affecting the polypeptide chain of the molecule. Their inheritance is X-chromosome linked. The instability of these TBGs at 37 degrees C may lead to more rapid degradation in vivo resulting in low nTBG and high dnTBG concentrations in serum.

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Selected References

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  1. Amino N., Hagen S. R., Yamada N., Refetoff S. Measurement of circulating thyroid microsomal antibodies by the tanned red cell haemagglutination technique: its usefulness in the diagnosis of autoimmune thyroid diseases. Clin Endocrinol (Oxf) 1976 Mar;5(2):115–125. doi: 10.1111/j.1365-2265.1976.tb02822.x. [DOI] [PubMed] [Google Scholar]
  2. BEIERWALTES W. H., ROBBINS J. Familial increase in the thyroxine-binding sites in serum alpha globulin. J Clin Invest. 1959 Oct;38:1683–1688. doi: 10.1172/JCI103946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burr W. A., Ramsden D. B., Hoffenberg R. Hereditary abnormalities of thyroxine-binding globulin concentration. A study of 19 kindreds with inherited increase or decrease of thyroxine-binding globulin. Q J Med. 1980;49(195):295–313. [PubMed] [Google Scholar]
  4. Daiger S. P., Rummel D. P., Wang L., Cavalli-Sforza L. L. Detection of genetic variation with radioactive ligands. IV. X-linked, polymorphic genetic variation of thyroxin-binding globulin (TBG). Am J Hum Genet. 1981 Jul;33(4):640–648. [PMC free article] [PubMed] [Google Scholar]
  5. Daiger S. P., Wildin R. S. Human thyroxine-binding globulin (TBG): heterogeneity within individuals and among individuals demonstrated by isoelectric focusing. Biochem Genet. 1981 Aug;19(7-8):673–685. doi: 10.1007/BF00484000. [DOI] [PubMed] [Google Scholar]
  6. Dick M., Watson F. A possible variant of thyroxine-binding globulin in Australian Aborigines. Clin Chim Acta. 1981 Nov 11;116(3):361–367. doi: 10.1016/0009-8981(81)90055-3. [DOI] [PubMed] [Google Scholar]
  7. Grimaldi S., Bartalena L., Ramacciotti C., Robbins J. Polymorphism of human thyroxine-binding globulin. J Clin Endocrinol Metab. 1983 Dec;57(6):1186–1192. doi: 10.1210/jcem-57-6-1186. [DOI] [PubMed] [Google Scholar]
  8. Gärtner R., Henze R., Horn K., Pickardt C. R., Scriba P. C. Thyroxine-binding globulin: investigation of microheterogeneity. J Clin Endocrinol Metab. 1981 Apr;52(4):657–664. doi: 10.1210/jcem-52-4-657. [DOI] [PubMed] [Google Scholar]
  9. Horwitz D. L., Refetoff S. Graves' disease associated with familial deficiency of thyroxine-binding globulin. J Clin Endocrinol Metab. 1977 Feb;44(2):242–247. doi: 10.1210/jcem-44-2-242. [DOI] [PubMed] [Google Scholar]
  10. Murata Y., Magner J. A., Refetoff S. The role of glycosylation in the molecular conformation and secretion of thyroxine-binding globulin. Endocrinology. 1986 Apr;118(4):1614–1621. doi: 10.1210/endo-118-4-1614. [DOI] [PubMed] [Google Scholar]
  11. Murata Y., Refetoff S., Sarne D. H., Dick M., Watson F. Variant thyroxine-binding globulin in serum of Australian aborigines: its physical, chemical and biological properties. J Endocrinol Invest. 1985 Jun;8(3):225–232. doi: 10.1007/BF03348482. [DOI] [PubMed] [Google Scholar]
  12. Murata Y., Takamatsu J., Refetoff S. Inherited abnormality of thyroxine-binding globulin with no demonstrable thyroxine-binding activity and high serum levels of denatured thyroxine-binding globulin. N Engl J Med. 1986 Mar 13;314(11):694–699. doi: 10.1056/NEJM198603133141107. [DOI] [PubMed] [Google Scholar]
  13. Refetoff S., Fang V. S., Marshall J. S., Robin N. I. Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess. J Clin Invest. 1976 Feb;57(2):485–495. doi: 10.1172/JCI108301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Refetoff S., Hagen S. R., Selenkow H. A. Estimation of the T 4 binding capacity of serum TBG and TBPA by a single T 4 load ion exchange resin method. J Nucl Med. 1972 Jan;13(1):2–12. [PubMed] [Google Scholar]
  15. Refetoff S., Murata Y., Vassart G., Chandramouli V., Marshall J. S. Radioimmunoassays specific for the tertiary and primary structures of thyroxine-binding globulin (TBG): measurement of denatured TBG in serum. J Clin Endocrinol Metab. 1984 Aug;59(2):269–277. doi: 10.1210/jcem-59-2-269. [DOI] [PubMed] [Google Scholar]
  16. Refetoff S., Murata Y. X-chromosome-linked inheritance of the variant thyroxine-binding globulin in Australian aborigines. J Clin Endocrinol Metab. 1985 Feb;60(2):356–360. doi: 10.1210/jcem-60-2-356. [DOI] [PubMed] [Google Scholar]
  17. Refetoff S., Robin N. I., Alper C. A. Study of four new kindreds with inherited thyroxine-binding globulin abnormalities. Possible mutations of a single gene locus. J Clin Invest. 1972 Apr;51(4):848–867. doi: 10.1172/JCI106880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Refetoff S., Selenkow H. A. Familial thyroxine-binding globulin deficiency in a patient with Turner's syndrome (XO). Genetic study of a kindred. N Engl J Med. 1968 May 16;278(20):1081–1087. doi: 10.1056/NEJM196805162782002. [DOI] [PubMed] [Google Scholar]
  19. Robbins J., Cheng S. Y., Gershengorn M. C., Glinoer D., Cahnmann H. J., Edelnoch H. Thyroxine transport proteins of plasma. Molecular properties and biosynthesis. Recent Prog Horm Res. 1978;34:477–519. doi: 10.1016/b978-0-12-571134-0.50017-x. [DOI] [PubMed] [Google Scholar]
  20. Robin N. I., Hagen S. R., Collaço F., Refetoff S., Selenkow H. A. Serum tests for measurement of thyroid function. Hormones. 1971;2(5):266–279. doi: 10.1159/000178240. [DOI] [PubMed] [Google Scholar]
  21. Takamatsu J., Ando M., Weinberg M., Refetoff S. Isoelectric focusing variant thyroxine-binding globulin in American blacks: increased heat lability and reduced serum concentration. J Clin Endocrinol Metab. 1986 Jul;63(1):80–87. doi: 10.1210/jcem-63-1-80. [DOI] [PubMed] [Google Scholar]

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