Summary
In this study we have carried out haplotype analysis on the β-globin gene cluster and characterized the β-thalassemia mutation by oligonucleotide hybridization in 14 patients with thalassemia major and 5 with sickle cell/β-thalassemia originating from southern Portugal. We found that three mutations, namely the β°-39, β° IVS-1 nt 1 and β+ IVS-1 nt 110 are prevalent accounting for 53%, 32% and 10% of the β-thalassemia chromosomes respectively. In general each mutation was associated with a specific chromosomal haplotype; the β° mutation, however, was linked to three different haplotypes. These results indicate that three oligo-probes complementary to the most common mutations allow prenatal diagnosis by oligonucleotide analysis in 96% of the couples at risk of having offspring with thalassemia major in southern Portugal.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akar N, Cavdar AO, Dessi E, Loi A Pirastu M, Cao A (1987) Beta-thalassemia mutations in Turkish population. J Med Genet 24: 378–379
Antonarakis SE, Boehm CD, Giardina PJV, Kazazian HH (1982) Nonrandom association of polymorphic restriction sites in the β-globin gene cluster. Proc Natl Acad Sci USA 79:137–141
Boehm CD, Antonarakis SE, Phillips JA III, Stetten G, Kazazian HH Jr (1983) Prenatal diagnosis using DNA polymorphisms. Report of 95 pregnancies at risk for sickle cell or β-thalassemia. N Engl J Med 308:1052–1058
Cao A, Pirastu M, Rosatelli C (1986) The prenatal diagnosis of thalassaemia. Br J Haematol 63:215–220
Cheng T-C, Orkin SH, Antonarakis SE, Potter MJ, Sexton JP, Markham AF, Giardina PJV, Li A, Kazazian HH (1984) β-thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc Natl Acad Sci USA 81:2821–2825
Conner BJ, Reyes AA, Morin C, Itakura K, Teplitz RL, Wallace RB (1983) Detection of sickle cell βS globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 80:278–282
Driscoll MC, Baird M, Bank A, Rachmilewitz EA (1981) A new polymorphism in the human β-globin gene: useful in antenatal diagnosis. J Clin Invest 68:915–919
Goossens M, Kan YW (1981) DNA analysis in the diagnosis of hemoglobin disorders. Methods Enzymol 76:805–817
Huang SZ, Law ML, Zeng YT, Zhang J, Kan YW (1986) β-thalassemia mutations in Chinese subjects identified by synthetic oligonucleotides. 7th International Congress of Human Genetics, Berlin, 1986, pt 1, p 661 (abstr)
Jeffreys A (1979) DNA sequence variants in Gγ, Aγ and β-globin genes of man. Cell 18:1–10
Kan YW, Lee KY, Furbetta M, Angius A, Cao A (1980) Polymorphism in DNA sequence in the β-globin region: application to prenatal diagnosis of β°-thalassemia in Sardina. N Engl J Med 302: 185–188
Kazazian HH, Orkin SH, Antonarakis SE, Sexton JP, Boehm CD, Goff SC, Waber PG (1984) Molecular characterization of seven β-thalassemia mutations in Asian Indians. EMBO J 3:593–596
Loi A, Pirastu M, Cao A, Ulbridh R, Hansmann I (1986) Prenatal diagnosis of most common Mediterranean β-thalassemia mutants. Lancet I:274
Orkin SH, Kazazian HH, Antonarakis SE, Goff SC, Boehm CD (1982) Linkage of β-thalassemia mutations and β-globin gene polymorphisms with DNA polymorphisms in the human β-globin gene cluster. Nature 296:627–631
Orkin SH, Marham AF, Kazazian HH (1983) Direct detection of the common Mediterranean β-thalassemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest 71:775–779
Pirastu M, Kan YW, Cao A, Conner BJ, Teplitz RL, Wallace RB (1983) Prenatal diagnosis of β-thalassemia: detection of a single nucleotide mutation in DNA. N Engl J Med 309:284–287
Pirastu M, Doherty M, Tuveri T, Cao A, Kan YW (1987) The same β-globin gene mutation is present on nine different β-thalassemia chromosomes in a Sardinian population. Proc Natl Acad Sci USA 84:2882–2885
Rosatelli C, Falchi AM, Scalas MT, Tuveri T, Di Tucci A, Monni G, Cao A (1985) Prenatal diagnosis of beta-thalassemia with the synthetic oligomer technique. Lancet I:241–243
Rosatelli C, Leoni GB, Tuveri T, Scalas MT, Di Tucci A, Cao A (1987) Thalassemia mutations in Sardinians: implication for prenatal diagnosis. J Med Genet 24:97–100
Tamagnini GP, Lopes MC, Castanheira ME, Wainscoat JS (1983) 15-2 Portuguese type: clinical, haematological and molecular studies of a newly defined from of β-thalassemia. Br J Haematol 54:189–200
Thein SL, Wainscoat JS, Old SM, Sampietro M, Fiorelli G, Wallace RB, Weatherall DJ (1985a) Feasibility of prenatal diagnosis of β-thalassemia with synthetic DNa probes in two Mediterranean populations. Lancet II:345–347
Thein SL, Wainscoat JS, Old JM, Wallace RB, Weatherall DJ (1985b) The AvaIl β-polymorphism is linked to the common Mediterranean β+-thalassemia mutation. Br J Haematol 61:747
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Coutinho Gomes, M.P., Gomes da Costa, M.G., Braga, L.B. et al. β-thalassemia mutations in the Portuguese population. Hum Genet 78, 13–15 (1988). https://doi.org/10.1007/BF00291226
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291226