Hemoglobinopathies

Czech version

Authors: Karel Indrák ¹; Martina Divoká ¹; Dagmar Pospíšilová ²; Jaroslav Čermák ³; Monika Beličková ³; Monika Horváthová ⁴; Vladimír Divoký ^1,4
Authors‘ workplace: Hemato-onkologická klinika LF UP a FN Olomouc ¹; Dětská klinika LF UP a FN Olomouc ²; Ústav hematologie a krevní transfuze, Praha ³; Ústav biologie LF UP Olomouc ⁴
Published in: Vnitř Lék 2018; 64(5): 476-487
Category:

Overview

This article summarize molecular-genetic basis of hemoglobinopathies, their classification and phenotypic manifestations. The description of individual subgroups is supplemented with a case reports of patients diagnosed in the Czech population. This paper provides an overview of 14 types of α-thalassemic mutations, 34 β-thalassemic alleles, 4 δβ-thalassemic alleles and 22 hemoglobin variants identified in the Czech population in 876 persons from 579 families. In more detail are described hemoglobinopathies, that have been diagnosed and described as novel: β-thalassemic mutation CD 38/39 (-C); Hb Olomouc; Hb Hana; Hb Hradec Kralove and 18.3 kb deletion downstream of α-globin cluster leading to a new mechanism of α-thalassemia-2. The fact that until the end of 2017 hemoglobinopathies were diagnosed in nearly 900 patients shows that they are not rare in the Czech Republic. This brings increased demands for their diagnostics, including prenatal diagnosis.

Key words:

hemoglobinopathies – hemoglobinopathy with high affinity to oxygen – sickle cell anemia – thalassemia – thalassemic hemoglobinopathy – unstable hemoglobins

Sources

Deisseroth A, Nienhuis A, Turner P et al. Localization of the human alpha-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assay. Cell 1977; 12(1): 205–218.
Deisseroth A, Nienhuis A, Lawrence J et al. Chromosomal localization of human beta globin gene on human chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci USA 1978; 75(3): 1456–1460.
Sgourou A, Routledge S, Antoniou M et al. Thalassaemia mutations within the 5‘UTR of the human beta-globin gene disrupt transcription. Br J Haematol 2004; 124(6): 828–835.
Divoká M, Partschová M, Pospíšilová D et al. Alfa-talasemie u 45 českých rodin a 37 rodin cizinců žijících v České republice: přehled literatury a molekulárně-genetická diagnostika. Transfuze Hematolo Dnes 2016; 22(3): 201–210.
Indrák K, Gu YC, Novotný J et al. 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.
Barbour VM, Tufarelli C, Indrak K et al. Alpha-thalassemia resulting from a negative chromosomal position effect. Blood 2000; 96(3): 800–807.
Sankaran VG, Weiss MJ. Anemia: progress in molecular mechanisms and therapies. Nat Med 2015; 21(3): 221–230. Dostupné z DOI: <http://dx.doi.org/10.1038/nm.3814>.
Divoky V, Svobodova M, Indrak K et al. Hb Hradec Kralove (Hb HK) or alpha2beta2 115 (G17) Ala→Asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family. Hemoglobin 1993; 17(4): 319–328.
Indrak K, Brabec V, Indrakova J et al. Molecular characterization of beta-thalassemia in Czechoslovakia. Hum Genet 1992; 88(4): 399–404.
Indrák K, Indráková J, Kutlar F et al. Compound heterozygosity for a beta zero-thalassemia (frameshift codons 38/39; – C) and a nondeletional Swiss type of HPFH (A-C at NT -ll0; G) in a Czechoslovakian family. Ann Hematol 1991; 63(2): 111–115.
Indrák K, Indráková J, Kutlarová F et al. Dvojnásobná heterozygozita pro beta thalassemii (posunutá mutace v kodonech 38/39:-C) a pro nedeleční – švýcarský – typ dědičné persistence hemoglobinu F (A-C v nukleotidu-110: ‚G‘gama) v olomoucké rodině. Hematológia a transfuziológia 1992; 2(1): 32–41.
Divoký V, Gu LH, Indrák K et al. A new beta zero-thalassemia nonsense mutation (codon 112, T-A) not associated with a dominant type of thalassemia in the heterozygote. Br J Haematol 1993; 83(3): 523–524.
Divoký V, Baysal E, Indrák K et al. The T-->C mutation at position +96 of the untranslated region 3‘ to the terminating codon of the beta-globin gene is a rare polymorphism that does not cause a beta-thalassemia as previously ascribed. Hum Genet 1994; 93(1): 77–78.
Divoká M, Partschova M, Kucerova J et al. Molecular Characterization of beta-Thalassemia in the Czech and Slovak Populations: Mediterranean, Asian and Unique Mutation. Hemoglobin 2016; 40(3): 156–162. Dostupné z DOI: <http://dx.doi.org/10.3109/03630269.2016.1152581>.
Steinberg MH, Adams JG. Thalassemic hemoglobinopathies. Am J Pathol 1983; 113(3): 396–409.
Wiedermann B, Indrák K, Wilson JB et al. Hb Saint Louis or alpha 2 beta 2(28)(B10)Leu----Gln in a Czechoslovakian male. Hemoglobin 1986; 10(6): 673–676.
Indrák K, Brabec V, Wilson JB et al. Hb Köln or alpha 2 beta 2(98)(FG5)Val----Met in a Czechoslovakian family. Hemoglobin 1991; 15(1–2): 133–135.
Divoký V, Indrák K, Divoká M et al. Hemoglobin Haná nebo alfa2 beta2 63 (E7) HIS-ASN: nová nestabilní varianta hemoglobinu identifikovaná v Moravské rodině z Hané. Vnitř Lék 1997; 43(5): 267–272.
Mojzikova R, Dolezel P, Pavlicek J et al. Partial glutathione reductase deficiency as a cause of diverse clinical manifestations in a family with unstable hemoglobin (Hemoglobin Haná, beta63(E7) His-Asn). Blood Cells Mol Dis 2010; 45(3): 219–222.
Charache S, Weatherall D, Clegg JB. Polycythemia associated with a hemoglobinopathy. J Clin Invest 1996; 45(6): 813–822. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI105397>.
Baxter EJ, Scott LM, Campbell PJ et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365(9464): 1054–1061. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(05)71142–9>. Erratum in Lancet 2005; 366(9480): 122.
James C, Ugo V, Le Couédic JP et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434(7037): 1144–1148. Dostupné z DOI: <http://dx.doi.org/10.1038/nature03546
Levine RL, Wadleigh M, Cools J et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7(4): 387–397. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ccr.2005.03.023>.
Kralovics R, Passamonti F, Buser AS et al. A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders. N Engl J Med 2005; 352(17): 1779–1790. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa051113>.
Indrák K, Wiedermann B, Bátěk F et al. Hb OLOMOUC or alpha2 beta2 86 /F2/ ALA-ASP, a new high oxygen affinity variant. Hemoglobin 1987; 11(2): 151–155.
Indrák K, Fei YJ, Li HW et al. A Czechoslovakian teenager with Hb E-beta zero-thalassemia [IVS-I-1 (G----A)] complicated by the presence of an alpha-globin gene triplication. Ann Hematol 1991; 63(1): 42–44.
Divoký V, Walczysková S, Pospíšilová D et al. Některé vzácnější formy hereditárních anémií vyskytující se v dospělé populaci v ČR – beta-talasemie a nestabilní hemoglobinové varianty. Vnitř Lék 2005; 91(7–8): 886–893.
Divoký V, Indrák K, Mojzíková R. Hemoglobinopatie: talasémie a strukturní Hb varianty. In: Pospíšilová Š, Dvořáková D, Mayer J (eds). Molekulární hematologie. Galén: Praha 2013: 270–283. ISBN 978–80–7262–942–8.