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. 1987 Feb;24(2):97–100. doi: 10.1136/jmg.24.2.97

Beta thalassaemia mutations in Sardinians: implications for prenatal diagnosis.

C Rosatelli, G B Leoni, T Tuveri, M T Scalas, A Di Tucci, A Cao
PMCID: PMC1049897  PMID: 3031299

Abstract

In this study we have characterised by oligonucleotide hybridisation and direct restriction endonuclease analysis the beta thalassaemia mutation in 494 Sardinian beta thalassaemia heterozygotes. The most prevalent mutation, accounting for 95.4% of the cases, was the nonsense mutation at codon 39. The remainder, in decreasing order of frequency, were a frameshift at codon 6 (2.2%), beta + IVS-1, nt 110 (0.4%), and beta + IVS-2, nt 745 (0.4%). This information allows prenatal diagnosis by DNA analysis to be made in the great majority of Sardinian couples at risk for beta thalassaemia.

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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. Baird M., Driscoll C., Schreiner H., Sciarratta G. V., Sansone G., Niazi G., Ramirez F., Bank A. A nucleotide change at a splice junction in the human beta-globin gene is associated with beta 0-thalassemia. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4218–4221. doi: 10.1073/pnas.78.7.4218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang J. C., Alberti A., Kan Y. W. A beta-thalassemia lesion abolishes the same Mst II site as the sickle mutation. Nucleic Acids Res. 1983 Nov 25;11(22):7789–7794. doi: 10.1093/nar/11.22.7789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conner B. J., Reyes A. A., Morin C., Itakura K., Teplitz R. L., Wallace R. B. Detection of sickle cell beta S-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci U S A. 1983 Jan;80(1):278–282. doi: 10.1073/pnas.80.1.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Driscoll M. C., Baird M., Bank A., Rachmilewitz E. A. A new polymorphism in the human beta-globin gene useful in antenatal diagnosis. J Clin Invest. 1981 Oct;68(4):915–919. doi: 10.1172/JCI110346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Kazazian H. H., Jr, Orkin S. H., Boehm C. D., Sexton J. P., Antonarakis S. E. beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. Am J Hum Genet. 1983 Sep;35(5):1028–1033. [PMC free article] [PubMed] [Google Scholar]
  9. Kazazian H. H., Jr, Orkin S. H., Markham A. F., Chapman C. R., Youssoufian H., Waber P. G. Quantification of the close association between DNA haplotypes and specific beta-thalassaemia mutations in Mediterraneans. Nature. 1984 Jul 12;310(5973):152–154. doi: 10.1038/310152a0. [DOI] [PubMed] [Google Scholar]
  10. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Goff S. C., Boehm C. D., Sexton J. P., Waber P. G., Giardina P. J. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. doi: 10.1038/296627a0. [DOI] [PubMed] [Google Scholar]
  11. Orkin S. H., Markham A. F., Kazazian H. H., Jr Direct detection of the common Mediterranean beta-thalassemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest. 1983 Mar;71(3):775–779. doi: 10.1172/JCI110826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pirastu M., Kan Y. W., Cao A., Conner B. J., Teplitz R. L., Wallace R. B. Prenatal diagnosis of beta-thalassemia. Detection of a single nucleotide mutation in DNA. N Engl J Med. 1983 Aug 4;309(5):284–287. doi: 10.1056/NEJM198308043090506. [DOI] [PubMed] [Google Scholar]
  13. Rosatelli C., Falchi A. M., Tuveri T., Scalas M. T., Di Tucci A., Monni G., Cao A. Prenatal diagnosis of beta-thalassaemia with the synthetic-oligomer technique. Lancet. 1985 Feb 2;1(8423):241–243. doi: 10.1016/s0140-6736(85)91026-8. [DOI] [PubMed] [Google Scholar]
  14. Thein S. L., Wainscoat J. S., Old J. M., Sampietro M., Fiorelli G., Wallace R. B., Weatherall D. J. Feasibility of prenatal diagnosis of beta-thalassaemia with synthetic DNA probes in two Mediterranean populations. Lancet. 1985 Aug 17;2(8451):345–347. doi: 10.1016/s0140-6736(85)92493-6. [DOI] [PubMed] [Google Scholar]
  15. Treisman R., Proudfoot N. J., Shander M., Maniatis T. A single-base change at a splice site in a beta 0-thalassemic gene causes abnormal RNA splicing. Cell. 1982 Jul;29(3):903–911. doi: 10.1016/0092-8674(82)90452-4. [DOI] [PubMed] [Google Scholar]
  16. Wallace R. B., Schold M., Johnson M. J., Dembek P., Itakura K. Oligonucleotide directed mutagenesis of the human beta-globin gene: a general method for producing specific point mutations in cloned DNA. Nucleic Acids Res. 1981 Aug 11;9(15):3647–3656. doi: 10.1093/nar/9.15.3647. [DOI] [PMC free article] [PubMed] [Google Scholar]

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