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. 1983 Aug;72(2):602–609. doi: 10.1172/JCI111008

Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster.

M Pirastu, Y W Kan, C C Lin, R M Baine, C T Holbrook
PMCID: PMC1129218  PMID: 6308057

Abstract

We describe a new type of gamma delta beta-thalassemia in four generations of a family of Scotch-Irish descent. The proposita presented with hemolytic disease of the newborn, which was characterized by a microcytic anemia. Initial restriction endonuclease analysis of the DNA showed no grossly abnormal patterns, but studies of polymorphic restriction sites and gene dosage revealed an extensive deletion that removed all the beta- and beta-like globin genes from the affected chromosome. In situ hybridization of chromosome preparations with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster in the affected family members.

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Selected References

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

  1. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernards R., Flavell R. A. Physical mapping of the globin gene deletion in hereditary persistence of foetal haemoglobin (HPFH). Nucleic Acids Res. 1980 Apr 11;8(7):1521–1534. doi: 10.1093/nar/8.7.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Deisseroth A., Nienhuis A., Lawrence J., Giles R., Turner P., Ruddle F. H. Chromosomal localization of human beta globin gene on human chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1456–1460. doi: 10.1073/pnas.75.3.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fritsch E. F., Lawn R. M., Maniatis T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature. 1979 Jun 14;279(5714):598–603. doi: 10.1038/279598a0. [DOI] [PubMed] [Google Scholar]
  6. Fritsch E. F., Lawn R. M., Maniatis T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell. 1980 Apr;19(4):959–972. doi: 10.1016/0092-8674(80)90087-2. [DOI] [PubMed] [Google Scholar]
  7. Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
  8. Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
  9. Kan Y. W., Forget B. G., Nathan D. G. Gamma-beta thalassemia: a cause of hemolytic disease of the newborn. N Engl J Med. 1972 Jan 20;286(3):129–134. doi: 10.1056/NEJM197201202860304. [DOI] [PubMed] [Google Scholar]
  10. Kan Y. W., Lee K. Y., Furbetta M., Angius A., Cao A. Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia. N Engl J Med. 1980 Jan 24;302(4):185–188. doi: 10.1056/NEJM198001243020401. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Kaufman R. E., Kretschmer P. J., Adams J. W., Coon H. C., Anderson W. F., Nienhuis A. W. Cloning and characterization of DNA sequences surrounding the human gamma-, delta-, and beta-globin genes. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4229–4233. doi: 10.1073/pnas.77.7.4229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lebo R. V., Carrano A. V., Burkhart-Schultz K., Dozy A. M., Yu L. C., Kan Y. W. Assignment of human beta-, gamma-, and delta-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5804–5808. doi: 10.1073/pnas.76.11.5804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lin C. C., van de Sande H., Smink W. K., Newton D. R. Quinacrine fluorescence and Q-banding patterns of human chromosomes. I. Effects of varying factors. Can J Genet Cytol. 1975 Mar;17(1):81–92. doi: 10.1139/g75-009. [DOI] [PubMed] [Google Scholar]
  15. Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A. Chromosomal localization of a single copy gene by in situ hybridization--human beta globin genes on the short arm of chromosome 11. Ann Hum Genet. 1981 May;45(Pt 2):135–141. doi: 10.1111/j.1469-1809.1981.tb00315.x. [DOI] [PubMed] [Google Scholar]
  16. Orkin S. H., Goff S. C., Nathan D. G. Heterogeneity of DNA deletion in gamma delta beta-thalassemia. J Clin Invest. 1981 Mar;67(3):878–884. doi: 10.1172/JCI110105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Orkin S. H., Kolodner R., Michelson A., Husson R. Cloning and direct examination of a structurally abnormal human beta 0-thalassemia globin gene. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3558–3562. doi: 10.1073/pnas.77.6.3558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ottolenghi S., Giglioni B., Comi P., Gianni A. M., Polli E., Acquaye C. T., Oldham J. H., Masera G. Globin gene deletion in HPFH, delta (o) beta (o) thalassaemia and Hb Lepore disease. Nature. 1979 Apr 12;278(5705):654–657. doi: 10.1038/278654a0. [DOI] [PubMed] [Google Scholar]
  19. Owerbach D., Bell G. I., Rutter W. J., Brown J. A., Shows T. B. The insulin gene is located on the short arm of chromosome 11 in humans. Diabetes. 1981 Mar;30(3):267–270. doi: 10.2337/diab.30.3.267. [DOI] [PubMed] [Google Scholar]
  20. Tuan D., Murnane M. J., deRiel J. L., Forget B. G. Heterogeneity in the molecular basis of hereditary persistence of fetal haemoglobin. Nature. 1980 May 29;285(5763):335–337. doi: 10.1038/285335a0. [DOI] [PubMed] [Google Scholar]
  21. Van der Ploeg L. H., Konings A., Oort M., Roos D., Bernini L., Flavell R. A. gamma-beta-Thalassaemia studies showing that deletion of the gamma- and delta-genes influences beta-globin gene expression in man. Nature. 1980 Feb 14;283(5748):637–642. doi: 10.1038/283637a0. [DOI] [PubMed] [Google Scholar]
  22. Weatherall D. J., Clegg J. B. Thalassemia revisited. Cell. 1982 May;29(1):7–9. doi: 10.1016/0092-8674(82)90084-8. [DOI] [PubMed] [Google Scholar]

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