Alpha-thalassemia in 45 Czech and 37 immigrant families: review of the literature and molecular diagnosis
Authors:
M. Divoká 1; M. Partschová 2; D. Pospíšilová 3; M. Orviská 1; A. Lapčíková 1; K. Indrák 1; J. Čermák 4; V. Divoký 1,2
Authors‘ workplace:
Hemato-onkologická klinika, Lékařská fakulta Univerzity Palackého a Fakultní nemocnice Olomouc
1; Ústav biologie, Lékařská fakulta Univerzity Palackého v Olomouci
2; Dětská klinika, Lékařská fakulta Univerzity Palackého v Olomouci a Fakultní nemocnice Olomouc
3; Ústav hematologie a krevní transfuze, Praha
4
Published in:
Transfuze Hematol. dnes,22, 2016, No. 3, p. 201-209.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Alpha-thalassemia is the most common monogenic gene disorder in the world. It is an inherited autosomal recessive disorder characterized by reduced production of the α-globin chains of hemoglobin. It belongs, together with other types of thalassemias and hemoglobinopathies, to common globin gene disorders widely distributed due to their natural selection through protection of carriers against severe malaria. Alpha-thalassemia most frequently results from deletions removing segments of DNA from the α-globin gene cluster on chromosome 16 and is characterized by a microcytic hypochromic anemia, with a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Alpha-thalassemia is especially frequent in populations originating from the South East Asia, Mediterranean region, Africa and Indian subcontinent, with rare occurrence in Central Europe. However, also in our region the presence of α-thalassemia should be considered as a possible cause of hereditary microcytic anemia. Specialized diagnostic approaches that are needed for correct diagnosis of α-thalassemia involve molecular analysis required to confirm the hematological and biochemical observations. The aim of this study is to report the variable phenotype and genotype of these disease states in the Czech families and in immigrants living in the Czech Republic.
KEY WORDS:
hemoglobinopathy – α-thalassemia – HbH disease – molecular diagnostics
Sources
1. Piel FB, Weatherall DJ. The α-thalassemias. N Engl J Med 2014; 371(20): 1908–1916.
2. Weatherall DJ, Williams TN, Allen SJ, O’Donnell A. The population genetics and dynamics of the thalassemias. Hematol Oncol Clin North Am 2010; 24(6): 1021–1031.
3. Indrák K, Divoký V, Brabec V, et al. Molekulárně genetická charakte-ristika α, α a αα thalassémií u 139 heterozygotů z 56 nepříbuzných rodin českého a slovenského původu. Vnitř Lék 1993; 39(10): 969–978.
4. Indrak K, Brabec V, Indrakova J, et al. Molecular characterization of α-thalassemia in Czechoslovakia. Hum Genet 1992; 88(4): 399–404.
5. Divoký V., Walczysková S, Pospíšilová D, et al. Některé vzácnější formy hereditárních anémií vyskytující se v dospělé populaci v ČR a SR – α-talasemie a nestabilní hemoglobinové varianty. Vnitř Lék 2005; 51: 741–748.
6. Divoka M, Partschova M, Kucerova J, et al. Molecular Characterization of b-Thalassemia in the Czech and Slovak Populations: Mediterranean, Asian and Unique Mutations. Hemoglobin 2016: 1–7. DOI: 10.3109/03630269.2016.1152581.
7. Barbour VM, Tufarelli C, Sharpe JA, et al. α-thalassemia resulting from a negative chromosomal position effect. Blood, 2000; 96(3): 800–807.
8. Tufarelli C, Stanley JA, Garrick D, et al. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat Genet 2003; 34(2): 157–165.
9. Divoký V, Indrák K, Mojzíková R. Hemoglobinopatie: talasémie a strukturální Hb varianty. In: Molekulární hematologie. Praha: Galén, 2013, s. 270– 283. ISBN 978-80-7262-942-8.
10. Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis 2010; 5: 13. DOI: 10.1186/1750-1172-5-13.
11. Chui DH. Alpha-thalassemia: Hb H disease and Hb Barts hydrops fetalis. Ann N Y Acad Sci 2005; 1054: 25–32.
12. Higgs DR, Buckle VJ, Gibbons R, Steensma D. Unusual Types of αThalassemia. In Steinberg MH, Forget BG, Higgs DR, Weatherall DJ. (Eds). Disorders of hemoglobin: genetics, pathophysiology and clinical management, 2nd edition. Cambridge: Cambridge University Press, 2009, s. 296–320.
13. Higgs DR. The molecular basis of α thalassemia. In Steinberg MH, Forget BG, Higgs DR, Weatherall DJ. (Eds). Disorders of hemoglobin: genetics, pathophysiology and clinical management, 2nd edition. Cambridge: Cambridge University Press, 2009, s. 241–265.
14. Lam KW, Jeffreys AJ. Processes of de novo duplication of human α-globin genes. Proc Natl Acad Sci USA 2007; 104(26): 10950–10955.
15. Indrak K, Fei YJ, LI HW, et al. A Czechoslovakian teenager with Hb E-ß0-thalassemia [IVS-I-1 (G→A)] complicated by the presence of an a-globin gene triplication. Ann Hematol 1991; 63(1): 42–44.
16. Indrak K, Gu YC, Novotny J, Huisman TH. A new alpha-thalassemia-2 deletion resulting in microcytosis and hypochromia and in vitro chain imbalance in the heterozygote. Am J Hematol, 1993; 43(2): 144–145.
17. De Gobbi M, Viprakasit V, Hughes JR, et al. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 2006; 312(5777): 1215–1217.
18. Clegg JB, Weatherall DJ. Haemoglobin synthesis in alpha-thalassaemia (haemoglobin H disease). Nature 1967; 215: 1241–1243.
19. Chong SS, Boehm CD, Higgs DR, Cutting GR. Single-tube multiplex-PCR screen for common deletional determinants of α-thalassemia. Blood 2000; 95(1): 360–362.
20. Harteveld CL, Voskamp A, Phylipsen M, et al. Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterised by high resolution multiplex ligation-dependent probe amplification. J Med Genet 2005; 42(12): 922–931.
21. Sulovska L, Holub D, Zidova Z, et al. Characterization of iron metabolism and erythropoiesis in erythrocyte membrane defects and thalassemia traits. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015. DOI: 10.5507/bp.2015.054. [Epub ahead of print]
22. Indrak K, Fei Y-J, Li H-W, et al. A Czechoslovakian teenager with Hb E- β0-thalassemia [IVS-I-1 (G→A)] complicated by the presence of an α-globin gene triplication. Ann Hematol 1991; 63(1): 42–44.
23. Orkin SH, Goff SC, Hechtman RL. Mutation in an intervening sequence splice junction in man. Proc Natl Acad Sci USA 1981; 78(8): 5041–5045.
Labels
Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
2016 Issue 3
Most read in this issue
- Alpha-thalassemia in 45 Czech and 37 immigrant families: review of the literature and molecular diagnosis
- Diagnosis and prognostic factors in mantle cell lymphoma
- Immunogenetic factors influencing red blood cell alloimmunization
- Correlation analysis of standard Bethesda method versus modified Nijmegen assay in detecting factor VIII inhibitors, and impact of marginal titer inhibitors on FVIII pharmacodynamics and pharmacokinetics by patients with hemophilia A