Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 Apr;49(4):635–642. doi: 10.1172/JCI106274

Mild thalassemia: the result of interactions of alpha and beta thalassemia genes

Yuet Wai Kan 1,2, David G Nathan 1,2
PMCID: PMC322517  PMID: 5443168

Abstract

Homozygous thalassemia is due to inherited unbalanced synthesis of the α- or β-chains of hemoglobin. Clinical severity may be in part related to the extent of α:β imbalance. Two families are presented that illustrate this concept. Thalassemia in these individuals was evaluated by clinical and genetic criteria. The relative rates of α- and β-chain synthesis in their reticulocytes were estimated by the extent of incorporation of 1-leucine—U-14C into the chains. Unusual combinations of clinical and hematological data and biosynthetic ratios were obtained in certain individuals which indicated the presence of combinations of α- and β-thalassemia genes. The propositus of the first family had mild Cooley's anemia and was believed to have one α- as well as two β-thalassemia genes. Presumably the α-thalassemia gene interfered with α-chain production which lead to less accumulation of α-chains and a reduced rate of intramedullary and peripheral hemolysis. In the second family two individuals were believed to have an α-thalassemia, a “silent carrier,” and a β-thalassemia gene. Despite the fact that they appeared to have the genotype of hemoglobin H disease, their cells contained no hemoglobin H and had a normal lifespan presumably because excess β-chain production was inhibited by the β-thalessemia gene. These family studies suggest that the α:β imbalance observed in thalassemia may be favorably influenced by combinations of α- and β-thalassemia genes.

Full text

PDF
635

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bank A., Braverman A. S., O'Donnell J. V., Marks P. A. Absolute rates of globin chain synthesis in thalassemia. Blood. 1968 Feb;31(2):226–233. [PubMed] [Google Scholar]
  2. Clegg J. B., Naughton M. A., Weatherall D. J. An improved method for the characterization of human haemoglobin mutants: identification of alpha-2-beta-2-95GLU, haemoglobin N (Baltimore). Nature. 1965 Aug 28;207(5000):945–947. doi: 10.1038/207945a0. [DOI] [PubMed] [Google Scholar]
  3. Fessas P., Loukopoulos D., Kaltsoya A. Peptide analysis of the inclusions of erythroid cells in beta-thalassemia. Biochim Biophys Acta. 1966 Aug 24;124(2):430–432. doi: 10.1016/0304-4165(66)90216-9. [DOI] [PubMed] [Google Scholar]
  4. Fessas P., Yatachanas X. Intraerythroblastic instability of hemoglobin beta-4 (Hgb H). Blood. 1968 Mar;31(3):323–331. [PubMed] [Google Scholar]
  5. GABUZDA T. G., NATHAN D. G., GARDNER F. H. THALASSEMIA TRAIT. GENETIC COMBINATIONS OF INCREASED FETAL AND A2 HEMOGLOBINS. N Engl J Med. 1964 Jun 4;270:1212–1217. doi: 10.1056/NEJM196406042702302. [DOI] [PubMed] [Google Scholar]
  6. GOUTTAS A., FESSAS P., TSEVRENIS H., XEFTERI E. Description d'une nouvelle variété d'anémie hémolytique congénitale; etude hématologique, électrophorétique et génétique. Sang. 1955;26(9):911–919. [PubMed] [Google Scholar]
  7. Gabuzda T. G., Nathan D. G., Gardner F. H. THE TURNOVER OF HEMOGLOBINS A, F, AND A(2) IN THE PERIPHERAL BLOOD OF THREE PATIENTS WITH THALASSEMIA. J Clin Invest. 1963 Nov;42(11):1678–1688. doi: 10.1172/JCI104854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HEYWOOD J. D., KARON M., WEISSMAN S. AMINO ACIDS: INCORPORATION INTO ALPHA- AND BETA-CHAINS OF HEMOGLOBIN BY NORMAL AND THALASSEMIC RETICULOCYTES. Science. 1964 Oct 23;146(3643):530–531. doi: 10.1126/science.146.3643.530. [DOI] [PubMed] [Google Scholar]
  9. INGRAM V. M., STRETTON A. O. Genetic basis of the thalassaemia diseases. Nature. 1959 Dec 19;184:1903–1909. doi: 10.1038/1841903a0. [DOI] [PubMed] [Google Scholar]
  10. Jacob H. S., Brain M. C., Dacie J. V. Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital Heinz body hemolytic anemia. J Clin Invest. 1968 Dec;47(12):2664–2677. doi: 10.1172/JCI105950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kan Y. W., Allen A., Lowenstein L. Hydrops fetalis with alpha thalassemia. N Engl J Med. 1967 Jan 5;276(1):18–23. doi: 10.1056/NEJM196701052760103. [DOI] [PubMed] [Google Scholar]
  12. Kan Y. W., Schwartz E., Nathan D. G. Globin chain synthesis in the alpha thalassemia syndromes. J Clin Invest. 1969 Nov;47(11):2512–2522. doi: 10.1172/JCI105933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nathan D. G., Gunn R. B. Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med. 1966 Nov;41(5):815–830. doi: 10.1016/0002-9343(66)90039-8. [DOI] [PubMed] [Google Scholar]
  14. Nathan D. G., Stossel T. B., Gunn R. B., Zarkowsky H. S., Laforet M. T. Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia. J Clin Invest. 1969 Jan;48(1):33–41. doi: 10.1172/JCI105972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pearson H. A. Alpha-beta thalassemia disease in a Negro family. N Engl J Med. 1966 Jul 28;275(4):176–181. doi: 10.1056/NEJM196607282750402. [DOI] [PubMed] [Google Scholar]
  16. RIGAS D. A., KOLER R. D., OSGOOD E. E. Hemoglobin H; clinical, laboratory, and genetic studies of a family with a previously undescribed hemoglobin. J Lab Clin Med. 1956 Jan;47(1):51–64. [PubMed] [Google Scholar]
  17. Rifkind R. A. Destruction of injured red cells in vivo. Am J Med. 1966 Nov;41(5):711–723. doi: 10.1016/0002-9343(66)90032-5. [DOI] [PubMed] [Google Scholar]
  18. SINGER K., CHERNOFF A. I., SINGER L. Studies on abnormal hemoglobins. II. Their identification by means of the method of fractional denaturation. Blood. 1951 May;6(5):429–435. [PubMed] [Google Scholar]
  19. Slater L. M., Muir W. A., Weed R. I. Influence of splenectomy on insoluble hemoglobin inclusion bodies in beta thalassemic erythrocytes. Blood. 1968 Jun;31(6):766–777. [PubMed] [Google Scholar]
  20. Todd D., Lai M. C., Braga C. A., Soo H. N. Alpha-thalassaemia in Chinese: cord blood studies. Br J Haematol. 1969 Jun;16(6):551–556. doi: 10.1111/j.1365-2141.1969.tb00436.x. [DOI] [PubMed] [Google Scholar]
  21. Todd D., Lai M., Braga C. A. Thalassaemia and hydrops foetalis-family studies. Br Med J. 1967 Aug 5;3(5561):347–349. doi: 10.1136/bmj.3.5561.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vigi V., Volpato S., Gaburro D., Conconi F., Bargellesi A., Pontremoli S. The correlation between red-cell survival and excess of alpha-globin synthesis in beta-thalassemia. Br J Haematol. 1969 Jan-Feb;16(1):25–30. doi: 10.1111/j.1365-2141.1969.tb00375.x. [DOI] [PubMed] [Google Scholar]
  23. WASI P., NA-NAKORN S., SUINGDUMRONG A. HAEMOGLOBIN H DISEASE IN THAILAND: A GENETICAL STUDY. Nature. 1964 Nov 28;204:907–908. doi: 10.1038/204907a0. [DOI] [PubMed] [Google Scholar]
  24. WEATHERALL D. J. BIOCHEMICAL PHENOTYPES OF THALASSEMIA IN THE AMERICAN NEGRO POPULATION. Ann N Y Acad Sci. 1964 Oct 7;119:450–462. doi: 10.1111/j.1749-6632.1965.tb54046.x. [DOI] [PubMed] [Google Scholar]
  25. Weatherall D. J., Clegg J. B., Naughton M. A. Globin synthesis in thalassaemia: an in vitro study. Nature. 1965 Dec 11;208(5015):1061–1065. doi: 10.1038/2081061a0. [DOI] [PubMed] [Google Scholar]
  26. Weissman S. M., Jeffries I., Karon M. The synthesis of alpha, beta, and delta peptide chains by reticulocytes from subjects with thalassemia or hemoglobin Lepore. J Lab Clin Med. 1967 Feb;69(2):183–193. [PubMed] [Google Scholar]
  27. Wennberg E., Weiss L. Splenic erythroclasia: an electron microscopic study of hemoglobin H disease. Blood. 1968 Jun;31(6):778–790. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES