Summary
We have identified different β-thalassemia mutations in 93 members of 34 families of Czech or Slovakian descent using gene amplification, hybridization with specific 32P-labeled oligonucleotide probes, sequencing of amplified DNA, and gene mapping. The G→A mutation at IVS-I-1 was found in 18 families; other Mediterranean mutations were IVS-II-1 (G→A), IVS-II-745 (C→G), IVS-I-110 (G→A), and codon 39 (C→T); these were present in 9 additional families. The G→T mutation at codon 121, known to cause Heinzbody β-thalassemia, was present in 3 families, and the frameshift at codons 82/83 (-G), first described in the Azerbaijanian population, in 2 families. A newly discovered allele was a frameshift at codons 38/39 (-C). One β-thalassemia allele was incompletely characterized. We observed in 2 families a T→C mutation at position +96 UTR (untranslated region) relative to the termination codon; this mutation likely is a rare polymorphism, α-Thalassemia was rare; only one person carried the -α3.7 heterozygosity, and one other had a yet to be identified α-thalassemia-1, while seven had the αααanti 3.7 triplication.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bissé E, Wieland H (1988) High-performance liquid chromatographic separation of human haemoglobins: simultaneous quantitation of foetal and glycated haemoglobins. J Chromatogr 434:95–110
Brabec V, Borova J, Fortova H, Hrodek O, Neuwirt J, Neuvirtova R, Syristova E (1988) β-Thalassemia in Czech families. Int Med 34:979–988
Efremov GD, Huisman THJ (1983) The occurrence of α and β chain abnormal hemoglobins and β-thalassemia in European countries. In: Bowman JE (eds) Distribution and evolution of hemoglobin and globin loci, vol 4. Elsevier, Amsterdam, 315–344
Fei YJ, Kutlar F, Harris HF II, Wilson MM, Milana A, Sciacca P, Schiliro G, Masala B, Manca L, Altay C, Gurgey A, de Pablos JMa, Villegas A, Huisman THJ (1989a) A search for anomalies in the ζ, α,β, and γ globin gene arrangements in normal Black, Italian, Turkish, and Spanish newborns. Hemoglobin 13:45–65
Fei YJ, Stoming TA, Kutlar A, Huisman THJ, Stamatoyannopoulos G (1989b) One form of inclusion body β-thalassemia is due to a GAA→TAA mutation at codon 121 of the β chain. Blood 73:1075–1077
Felice AE, Cleek MP, McKie K, McKie V, Huisman THJ (1984) The rare α-thalassemia-1 of Blacks is a ζα-thalassemia-1 associated with a deletion of all α- and ζ-globin genes. Blood 63:1253–1257
Felice AE, Cleek MP, Marino EM, McKie K, McKie VC, Chang BK, Huisman THJ (1986) Different ζ globin gene deletions among Black Americans. Hum Genet 73:221–224
Fortova H, Suttnar J, Brabec V, Pavlik M (1991) Hb E [β26(B8) Glu→Lys] in a Czechoslovakian family. Hemoglobin 15:129–131
Gilman JG, Huisman THJ (1985) DNA sequence variation associated with elevated fetal Gγ globin production. Blood 66:783–787
Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, 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
Gonzalez-Redondo JM, Kattamis C, Huisman THJ (1989) Characterization of three types of β∘-thalassemia resulting from a partial deletion of the β-globin gene. Hemoglobin 13:377–392
Huisman THJ (1990) Frequencies of common β-thalassaemia alleles among different populations: variability in clinical severity. Br J Haematol 76:454–457
Indrak K, Wiedermann BF, Batek F, Wilson JB, Webber BB, Kutlar A, Huisman THJ (1987) Hb Olomouc or α2β286(F2) Ala→Asp, a new high oxygen affinity variant. Hemoglobin 11:151–155
Indrak K, Indrakova J, Brabec V, Chrobak V, Sakalova A, Jarosova M, Sulovska I, Cermak J, Fei YJ, Kutlar F, Baysal E, Stoming TA, Huisman THJ (1990) Identification of β-thalassemia mutations in Czechoslovakia. Blood 76 [suppl 1]:63a
Indrak K, Brabec V, Wilson JB, Webber BB, Huisman THJ (1991a) Hb Köln or α2β298(FG5)Val→Met in a Czechoslovakian family. Hemoglobin 15:133–135
Indrak K, Indrakova J, Kutlar F, Pospisilova D, Sulovska I, Baysal E, Huisman THJ (1991b) Compound heterozygosity for a β°-thalassaemia ] (frameshift codons 38/39; -C) and a nondeletional Swiss type of HPFH (A→C at nt -110, Gγ) in a Czechoslovakian family. Ann Hematol 63:1–5
Kazazian HH Jr, Boehm CD (1988) Molecular basis and prenatal diagnosis of β-thalassemia. Blood 72:1107–1116
Kazazian HH Jr, Orkin SH, Boehm CD, Goff SC, Wong C, Dowling CE, Newburger PE, Knowlton RG, Brown V, Donis-Keller H (1986) Characterization of a spontaneous mutation to a β-thalassemia allele. Am J Hum Genet 38:860–867
Kollia P, Gonzalez-Redondo JM, Stoming TA, Loukopoulos D, Politis C, Huisman THJ (1989) Frameshift codon 5 [FSC-5 (-CT)] thalassemia: a novel mutation detected in a Greek patient. Hemoglobin 13:597–604
Kutlar A (1990) β-Thalassemia repository. Hemoglobin 14:661–675
Kutlar F, Kutlar A, Huisman THJ (1986) Separation of normal and abnormal hemoglobin chains by reversed-phase high-performance liquid chromatography. J Chromatogr 357:147–153
Kutlar A, Kutlar F, Gu L-G, Mayson SM, Huisman THJ (1990) Fetal hemoglobin in normal adults and β-thalassemia heterozygotes. Hum Genet 85:106–110
Öner R, Altay Ç, Gurgey A, Aksoy M, Kilinç Y, Stoming TA, Reese AL, Kutlar A, Kutlar F, Huisman THJ (1990) β-Thalassemia in Turkey. Hemoglobin 14:1–13
Poncz M, Solowiejczk 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
Righetti PG (1986) Practical applification of isoelectricfocusing in hemoglobin separation and identification. In: Huisman THJ (eds) The hemoglobinopathies. (Methods in hematology, vol 15). Churchill Livingstone, Edinburgh, pp 47–70
Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA (1986) Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele specific oligonucleotide probes. Nature 324:163–166
Sanger F, Nicklen S, Coulson AR (1977) DNA sequences with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5469
Schleider CTH, Mayson SM, Huisman THJ (1977) Further modification of the microchromatographic determination of Hemoglobin A2. Hemoglobin 1:503–504
Schroeder WA, Huisman THJ (1980) The chromatography of hemoglobin. (Clinical and biochemical analysis, vol 9). Dekker, NewYork
Schwartz EI, Gol'tsov AA, Kaboev OK, Alexeev AA, Solovyev GYa, Surin VL, Lukianenko AV, Vinogradov SV, Berlin YuA (1989) A novel frameshift mutation causing thalassaemia in Azerbaijan. Nucleic Acids Res 17:3997
Shelton JR, Shelton JB, Schroeder WA (1984) High performance liquid chromatograhic separation of globin chains on a largepore C4 column. J Liq Chromatogr 7:1969–1977
Stamatoyannopoulos G, Woodson R, Papayannopoulos Th, Heywood D, Kurachi S (1974) Inclusion body β-thalassemia trait. N Engl J Med 290:939–943
Thein SL, Hesketh C, Taylor P, Temperley JJ, Hutchinson RM, Old JM, Wood WG, Clegg JB, Weatherall DJ (1990) Molecular basis for dominantly inherited inclusion body β-thalassemia. Proc Natl Acad Sci USA 87:3924–3928
Wiedermann BF, Indrak K, Wilson JB, Webber BB, Yang KG, Kutlar F, Kutlar A, Huisman THJ (1986) Hb Saint Louis or α2β228(B10)Leu→Gln in a Czechoslovakian male. Hemoglobin 10:673–676
Yamamoto K, Yamamoto K, Hattori Y, Yamashiro Y, Hoshitani M, Morishita M, Ohba Y, Katahira H, Karasawa M, Omine M, Narukiyo T, Hirabayashi K, Miyawaki S (1991) Two β-thalassemia mutations, codon 121 (GAA→TAA) and IVS-I-130 (G→C) found in the Japanese population. Hemoglobin (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Indrak, K., Brabec, V., Indrakova, J. et al. Molecular characterization of β-thalassemia in Czechoslovakia. Hum Genet 88, 399–404 (1992). https://doi.org/10.1007/BF00215673
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00215673