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Sickle cell anemia, sickle cell β-thalassemia, and thalassemia major in Albania: characterization of mutations

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Abstract

We have analyzed the hemoglobin abnormalities in nearly 50 Albanian patients with a significant hemoglobinopathy and included 37 relatives in this study. Sickle cell anemia (SS) is a common disorder; all 15 sickle cell anemia patients had the complications expected for this disease. The βs haplotype was type 19 (Benin); α-thalassemia-2 was rare. Three β-thalassemia alleles (IVS-I-110, G→A; codon 39, C→T; IVS-I-6, T→C) were present in nearly 85% of the β-thalassemia alleles; their frequencies were intermediate between those observed in the populations of neighboring countries. A few rare mutations were also found, which might have originated in India, Turkey, Macedonia, and Greece. Nearly all patients with Hb S-β-thalassemia had the IVS-I-110 (G→A) mutation. The frequencies of 11 β-thalassemia mutations in 17 mostly Mediterranean countries have been reviewed.

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References

  • Amselem S, Nunes V, Viadaud M, Estiville X, Wong C, D'Auriol L, Vidaud D, Galibert F, Baiget M, Goosens M (1988) Determination of the spectrum of β-thalassemia genes in Spain by use of dot-blot analysis of amplified β-globin DNA. Am J Hum Genet 43:95–100

    Google Scholar 

  • Ashta A (1961) Malaria ne shqiperi. Botim I U Sh T, Tirane 1961

  • Başak AN, Ozçelik H, Ozer A, Tolun A, Aksoy M, Agaoglu L, Ridolf F, Ulukutlu L, Akar N, Gürgey A, Kirdar B (1992) The molecular basis of β-thalassemia in Turkey. Hum Genet 89:315–318

    Google Scholar 

  • Baysal E, Huisman THJ (1994) Detection of common deletional α-thalassemia-2 determinants by PCR. Am J Hematol (in press)

  • Baysal E, Indrak K, Bozkurt G, Berkalp A, Artikan E, Old JM, Ioannou P, Angastiniotis M, Droushiotou A, Yüregir GT, Kilinç Y, Huisman THJ (1992) The β-thalassemia mutations in the population of Cyprus. Br J Haematol 81:607–609

    Google Scholar 

  • Bissé E, Wieland H (1988) High-performance liquid chromatographic separation of human haemoglobins: simultaneous quantitation of foetal and glycated haemoglobin. J Chromatogr 434:95–110

    Google Scholar 

  • Boletini E (1983) A new electrophoretic method for the diagnosis of hemoglobinopathies (in Albanian). Nena dhe Femia 2:49–52

    Google Scholar 

  • Boletini E (1991) The haemoglobinopathies in Albania. Proceedings of the Meeting of the Mediterranean Blood Club, Milan, Italy. pp 9–11

  • Boletini E, Duka D (1992) A comparison of Silvestroni-Bianco disease (sickle-cell/beta-thalassemia) in Albania. 30th Italian Congress of Transfusion Medicine, Rome. Hemoglobinopathies PO 192

  • Boussiou M, Loukopoulos D, Christakis J, Fessas P (1991) The origin of the sickle mutation in Greece: evidence from βs globin gene cluster polymorphisms. Hemoglobin 15:459–467

    Google Scholar 

  • Chehab FF, Der Kaloustian V, Khouri FP, Deeb SS, Kan YW (1987) The molecular basis of β-thalassemia in Lebanon. Blood 69:1141–1145

    Google Scholar 

  • Coutinho Gomes MP, Gomes da Costa MG, Braga LB, Cordeiro-Ferrera NT, Lot A, Pirastu M, Cao A (1988) β-Thalassemia mutations in the Portuguese population. Hum Genet 78:13–15

    Google Scholar 

  • Cürük MA, Yüregir GT, Asadov CD, Dadasova T, Gu L-H, Baysal E, Gu Y-C Ribeiro MLS, Huisman THJ (1992) Molecular characterization of β-thalassemia in Azerbaijan. Hum Genet 90:417–419

    Google Scholar 

  • Diaz-Chico JC, Yang KG, Stoming TA, Efremov DG, Kutlar A, Kutlar F, Aksoy M, Altay Ç, Gürgey A, Huisman THJ (1988) Mild and severe β-thalassemia among homozygotes from Turkey: identification of the types by hybridization of amplified DNA with synthetic probes. Blood 71:248–251

    Google Scholar 

  • Dimovski A, Efremov DG, Jankovic L, Juricic D, Zisovski N, Stojanovski N, Nikolov N, Petkov GT, Reese AL, Stoming TA, Efremov GD, Huisman THJ (1990) β-Thalassemia in Yugoslavia. Hemoglobin 14:15–24

    Google Scholar 

  • Efremov GD, Juricic D, Petkov GH, Huisman THJ (1992) β-Thalassemia in Yugoslavia and Bulgaria. Hematol Rev 6:83–95

    Google Scholar 

  • Fattoum S, Guemira F, Öner C, Öner R, Li H-W, Kutlar F, Huisman THJ (1991) β-Thalassemia, Hb S-β-thalassemia and sickle cell anemia among Tunisians. Hemoglobin 15:11–21

    Google Scholar 

  • Faustino P, Osorio-Almeida L, Barbot J, Espirito-Santo D, Goncalves J, Romao L, Martins MC, Marques MM, Lavinha J (1992) Novel promoter and splice junction defects add to the genetic, clinical or geographic heterogeneity of β-thalassemia in the Portuguese population. Hum Genet 89:573–576

    Google Scholar 

  • Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, Kutlar F, Nakatsuji T, Deng B, Han IS, McKie VC, Huisman THJ (1988) Clinical and genetic heterogeneity in black patients with homozygous β-thalassemia from the southeastern United States. Blood 72:1007–1014

    Google Scholar 

  • Gürgey A, Altay Ç, Diaz-Chico JC, Kutlar F, Kutlar A, Huisman THJ (1989) Molecular heterogeneity of β-thalassemia intermedia in Turkey. Acta Haematol 81:22–27

    Google Scholar 

  • Huisman THJ (1990) Frequencies of common β-thalassaemia alleles among different populations: variability in clinical severity. Br J Haematol 76:454–457

    Google Scholar 

  • Indrak K, Brabec V, Indrakova J, Chrobak L, Sakalova A, Jarosova M, Cermak J, Fei Y-J, Kutlar F, Gu Y-C, Baysal E, Huisman THJ (1992) Molecular characterization of β-thalassemia in Czechoslovakia. Hum Genet 88:399–404

    Google Scholar 

  • Kalaydjieva L, Eigel A, Horst J (1989) The molecular basis of β-thalassemia in Bulgaria. J Med Genet 26:614–618

    Google Scholar 

  • Kattamis C, Hu H, Cheng G, Reese AL, Gonzalez-Redondo JM, Kutlar A, Kutlar F, Huisman THJ (1990) Molecular characterization of β-thalassaemia in 174 Greek patients with thalassaemia major. Br J Haematol 74:342–346

    Google Scholar 

  • Kinniburgh AJ, Maquat LE, Schedl T, Rachmilewitz R, Ross J (1982) mRNA-deficient β°-thalassemia results from a single nucleotide deletion. Nucleic Acids Res 10:5421–5427

    Google Scholar 

  • Kollia P, Karababa Ph, Sinopulou K, Voskaridou E, Boussiou M, Papadakis M, Loukopoulos D (1992) β-Thalassemia mutations and associated RFLPs in the Greek population. In: Roath S, Huisman THJ (eds) Current views on thalassemia, with special reference to its Mediterranean presence. Harwood Academic Publishers, London, pp 97–100

    Google Scholar 

  • Kutlar A, Kutlar A, Huisman THJ (1986) Separation of normal and abnormal hemoglobin chains by reversed-phase high-performance liquid chromatography. J Chromatogr 357:147–153

    Google Scholar 

  • Kutlar A, Kutlar F, Gu L-G, Mayson SM, Huisman THJ (1990) Fetal hemoglobin in normal adults and β-thalassemia heterozygotes. Hum Genet 86:106–110

    Google Scholar 

  • Labie D, Bennani C, Beldjord C (1990) β-Thalassemia in Algeria. Ann N Y Acad Sci 612:43–54

    Google Scholar 

  • Maggio A, Marzo R Di, Giambona A, Renda M, Acuto S, Gioco P Lo, D'Alcamo E, Trapani F Di, Marino M, Aate I, Sammarco P, Kazazian HH (1990) β-Thalassemia mutations in Sicily. Ann N Y Acad Sci 612:67–73

    Google Scholar 

  • Marzo R Di, Dowling CE, Wong C, Maggio A, Kazazian HH (1988) The spectrum of β-thalassemia mutations in Sicily. Br J Haematol 69:393–397

    Google Scholar 

  • Masala B (1992) Hemoglobinopathies in Sardinia. Hemoglobin 16:331–351

    Google Scholar 

  • Murru S, Loudianos G, Deiana M, Camaschella C, Sciarratta GB, Agosti S, Parodi MI, Ceruti P, Pirastu M (1991) Molecular characterization of β-thalassemia intermedia in patients of Italian descent and identification of three novel β-thalassemia mutations. Blood 77:1342–1347

    Google Scholar 

  • Nemeskeri J, Dhima A (1988) Sprove per rindertimin paleobiologik te popullsise apoloniake. Iliria 1:119–155

    Google Scholar 

  • Novelletto A, Hafez M, Deidda G, Rienzo A Di Felicetti L, El-Tahan H, El-Morsi Z, E-Ziny M, Al-Tonbary Y, Sittien A, Terrenato L (1990) Molecular characterization of β-thalassemia mutations in Egypt. Hum Genet 83:272–274

    Google Scholar 

  • Öner R, Altay C, Gurgey A, Aksoy M, Kilinc Y, Stoming TA, Reese AL, Kutlar A, Kutlar F, Huisman THJ (1990) β-Thalassemia in Turkey. Hemoglobin 14:1–13

    Google Scholar 

  • Öner C, Dimovski AJ, Olivieri NF, Schiliro G, Codrington JF, Fattoum S, Adekile AD, Öner R, Yüregir GT, Altay Ç, Gürgey A, Gupta RB, Jogessar VB, Kitundu MN, Loukopoulos D, Tamagnini GP, Ribeiro MLS, Kutlar F, Gu L-H, Lanclos KD, Huisman THJ (1992) βs Haplotypes in various world populations. Hum Genet 88:99–104

    Google Scholar 

  • Orkin SH, Kazazian HH Jr, Antonarakis SE, Goff SC, Boehm CD, Sexton JP, Waber PG, Giardina PJV (1982) Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster. Nature 296:627–631

    Google Scholar 

  • Petkov GH, Efremov GD, Efremov DG, Dimovski AJ, Tchaicarova P, Tchaicarov R, Rogina B, Agarwal S, Kutlar A, Kutlar F, Reese AL, Stoming TA, Huisman THJ (1990) β-Thalassemia in Bulgaria. Hemoglobin 14:25–33

    Google Scholar 

  • Pirastu M, Loudianos G, Murru S, Ristaldi SM, Cossu P, Pilia G, Porcu S, Vaccargiu S, Casu R, Deiana MCA (1992) β-Thalassemia in the Italian population. In: Roath S, Huisman THJ (eds) Current views on thalassemia. Harwood Academic Publishers, London, pp 101–112

    Google Scholar 

  • Poncz M, Solowiejczyk D, Harpel B, Mory Y, Schwartz E, Surrey S (1982) Construction of human gene libraries from small amounts of peripheral blood: analysis of β-like globin genes. Hemoglobin 6:27–36

    Google Scholar 

  • Ribeiro MLS, Baysal E, Kutlar F, Tamagnini GP, Goncalves P, Lopes D, Huisman THJ (1992) A novel β°-thalassemia mutation (codon 15, TGG→TGA) is prevalent in a population of central Portugal. Br J Haematol 80:567–568

    Google Scholar 

  • Righetti PG, Gianazza E, Bianchi-Bosisio A, Cossu G (1986) Conventional isoelectric focusing and immobilized pH gradients for hemoglobin separation and identification. In: Huisman THJ (ed) The hemoglobinopathies. (Methods in hematology, vol 15) Churchill Livingstone, Edinburgh, pp 47–70

    Google Scholar 

  • Ringelhann B, Szelenyi G, Horanyi M, Svobodova M, Divoky V, Indrak K, Huisman THJ (1993) Molecular characterization of β-thalassemia in Hungary. Hum Genet (in press)

  • Rosatelli MC, Leoni GB, Tuveri T, Scalas MT, Tucci A Di, Cao A (1987) β-Thalassemia mutations in Sardinians: implications for prenatal diagnosis. J Med Genet 24:97–100

    Google Scholar 

  • Rosatelli MC, Tuveri T, Scalas MT, Leoni GB, Raffaela Sardu, Valeria F, Meloni A, Pischedda MA, Demurtas M, Monni G, Cao A (1992) Molecular screening and fetal diagnosis of β-thalassemia in the Italian population. Hum Genet 89:585–589

    Google Scholar 

  • Rund D, Filon D, Dowling C, Kazazian HH, Rachmilewitz E, Oppenhein A (1990) Molecular studies of β-thalassemia in Israel. Ann NY Acad Sci 612:98–105

    Google Scholar 

  • Rund D, Cohen T, Filon D, Dowling CE, Warren TC, Barak I, Rachmilewitz E, Kazazian HH, Oppenheim A (1991) Evolution of a genetic disease in an ethnic isolate: β-thalassemia in the Jews of Kurdistan. Proc Natl Acad Sci USA 88:310–314

    Google Scholar 

  • Sanger F, Nicklen S, Coulson R (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5469

    CAS  PubMed  Google Scholar 

  • Schiliro G, Spena M, Giambelluca E, Maggio A (1990) Sickle hemoglobinopathies in Sicily. Am J Hematol 33:81–85

    Google Scholar 

  • Schiliro G, Samperi P, Testa R, Gupta RB, Gu L-H, Huisman THJ (1992) Clinical, hematological, and molecular features in Sicilians with Hb S-β-thalassemia. Am J Hematol 41:264–269

    Google Scholar 

  • Shelton JB, Shelton JR, Schroeder WA (1984) High performance liquid chromatographic separation of globin chains on a largepore C4 column. J Liquid Chromatogr 7:1969–1977

    Google Scholar 

  • Sözöüz A, Berkalp A, Figus A, Loi A, Pirastu M, Cao A (1988) β-Thalassemia mutations in Turkish Cypriots. J Med Genet 25:766–768

    Google Scholar 

  • Tamagnini GP, Goncalves P, Ribeiro MLS, Kaeda J, Kutlar F, Baysal E, Huisman THJ (1993) β-Thalassemia mutations in the Portuguese: high frequencies of two allleles in restricted populations. Hemoglobin 17:31–40

    Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical College of Georgia, 30912-2100, Augusta, GA, USA

    Enis Boletini, Martina Svobodova, Vladimir Divoky, Erol Baysal, Mehmet A. Cürük, Aleksandar J. Dimovski, Rong Liang, Adekunle D. Adekile & Titus H. J. Huisman

  2. Center of Hemoglobinopathies, Department of Clinical Biochemistry, Institute of Pediatrics, Tirana, Albania

    Enis Boletini

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  1. Enis Boletini
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  2. Martina Svobodova
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  3. Vladimir Divoky
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  4. Erol Baysal
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  5. Mehmet A. Cürük
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  6. Aleksandar J. Dimovski
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  8. Adekunle D. Adekile
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  9. Titus H. J. Huisman
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Boletini, E., Svobodova, M., Divoky, V. et al. Sickle cell anemia, sickle cell β-thalassemia, and thalassemia major in Albania: characterization of mutations. Hum Genet 93, 182–187 (1994). https://doi.org/10.1007/BF00210607

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  • DOI: https://doi.org/10.1007/BF00210607

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