Abstract
We describe the hematological and DNA characterization of hemoglobin (Hb) E heterozygote with various forms of α-thalassemia in Thai individuals. Altogether, 202 unrelated adult subjects with Hb E heterozygotes either with or without α-thalassemia determinant were studied. The most prevalent interaction was found to be a double heterozygote for Hb E/α-thalassemia 2, followed by a double Hb E/α-thalassemia 1 and a Hb E/Hb Constant Spring (CS), even though the Hb CS was not detected. Double heterozygotes for Hb E and homozygous α-thalassemia 2 and Hb E with a compound α-thalassemia 2/Hb CS were also encountered with lower frequencies. Unexpectedly, as many as 18 cases previously diagnosed as Hb E carriers at routine Hb analysis were indeed Hb E heterozygotes with compound α-thalassemia 1/α-thalassemia 2, indicating a need for globin genotyping for accurate diagnosis. A change in Hb E level was observed which was related to a concomitant inheritance of α-thalassemia. The hematological expression of these Hb E heterozygotes with various forms of α-thalassemia, including a hitherto undescribed condition of double heterozygosity for Hb E/Hb Paksé identified in two subjects, is presented comparatively with those of the 80 cases of pure Hb E carriers. A multiplex allele-specific polymerase chain reaction (PCR) assay for simultaneous detection of Hb E and Hb CS genes is also described.
Similar content being viewed by others
References
Chan LC, Ma SK, Chan AYY, HA SY, Waye JS, Lau YL, Chui DHK (1980) Should we screen for globin gene mutations in blood samples with mean corpuscular volume (MCV) greater than 80 fl in areas with a high prevalence of thalassemia? J Clin Pathol 54:317–320
Desai S, Colah R, Gubte S, Mohanty D (1997) Is cellulose acetate electrophoresis a suitable technique for detection of Hb Bart's at birth? Hum Hered 47:181–184
Fucharoen G, Fucharoen S (1994) Rapid and simultaneous non-radioactive method for detecting α-thalassemia 1 (SEA-type) and Hb Constant Spring genes. Eur J Haematol 53:186–187
Fucharoen S, Fucharoen G, Fukumaki Y (1990) Simple non-radioactive method for detecting hemoglobin Constant Spring gene. Lancet 335:1527
Fucharoen S, Shimizu K, Fukumaki Y (1990) A novel C-T transition within the distal CCAAT motif of theGγ-globin gene in the Japanese HPFH: implication of factor binding in elevated fetal globin expression. Nucleic Acids Res 18:5245–5253
Fucharoen S, Fucharoen G, Ratanasiri T, Jetsrisuparp A, Fukumaki Y (1994) A simple non-radioactive assay for hemoglobin E gene in prenatal diagnosis. Clin Chim Acta 229:197–203
Fucharoen S, Winichagoon P, Sirithanaratkul N, Chowthaworn J, Pootrakul P (1998) α- and β-thalassemia in Thailand. Ann N Y Acad Sci 850:412–414
Fucharoen S, Fucharoen G, Sanchaisuriya K, Pengjam Y (2002) Molecular analysis of a Thai β-thalassemia heterozygote with normal haemoglobin A2 level: implication for population screening. Ann Clin Biochem 39:44–49
Genesan J, Lie-Injo E, Ng TS, George R (1977) Interaction of haemoglobin E with α-thalassemia and hemoglobin Constant Spring. Acta Haematol 57:109–115
Higgs DR, Lamb J, Aldridge BE, Clegg JB, Weatherall DJ, Serjeant BE, Serjeant GR (1982) Inadequacy of Hb Bart's as an indicator of α-thalassaemia. Br J Haematol 51:177–179
Honig GR, Adams III JG (1986) Human hemoglobin genetics. Springer, Berlin Heidelberg New York, pp 191–193
Huisman THJ (1997) Hb E and α-thalassemia; variability in the assembly of βE chain containing tetramers. Hemoglobin 21:227–236
International Committee for Standardization in Hematology (1978) Recommendations for selected methods for quantitative estimation of Hb A2 and Hb A2 reference preparation. Br J Haematol 38:573–578
Kutlar F, Gu LH, Hu H, Huisman TH (1989) Quantitation of hemoglobins Bart's, H, Portland-I, Portland-II and Constant Spring by anion exchange high performance liquid chromatography. J Chromatogr 24:265–274
Orkin SH, Kazazian HHJr, Antonarakis SE, Ostrer H, Goff SC, Sexton JP (1982) Abnormal RNA processing due to the exon mutation of βE-globin gene. Nature 300:768–769
Panyasai S, Sringam P, Fucharoen G, Sanchaisuriya K, Fucharoen S (2002) A simplified screening for α-thalassemia 1 (SEA type) using a combination of a modified osmotic fragility test and a direct PCR on whole blood cell lysates. Acta Haematol 108:74–78
Papassotiriou I, Traeger-Synodinos J, Vlachou C, Karagiorga M, Metaxotou A, Kanavakis E, Stamoulakatou A (1999) Rapid and accurate quantitation of Hb Bart's and Hb H using weak cation exchange high performance liquid chromatography: correlation with the α-thalassemia genotype. Hemoglobin 23:203–211
Sanchaisuriya K, Fucharoen G, Sae-ung N, Baisungneon R, Jetsrisuparb A, Fucharoen S (1997) Molecular and hematological characterization of Hb E heterozygote with α-thalassemia determinant. Southeast Asian J Trop Med Public Health 28 [Suppl 3]:100–103
Sanchaisuriya K, Fucharoen G, Fucharoen S (2002) Hb Pakse′ [(α2) codon 142 (TAA-TAT) or Term-Tyr)] in Thai patients with EABart's disease and Hb H disease. Hemoglobin 26:227–235
Siriratmanawong N, Fucharoen G, Sanchaisuriya K, Ratanasiri T, Fucharoen S (2001) Simultaneous PCR detection of β-thalassemia and α-thalassemia 1 (SEA type) in prenatal diagnosis of complex thalassemia syndrome. Clin Biochem 34:377–380
Viprakasit V, Tanphaichitr VS, Pung-Amarit P, Petrarat S, Suwanthol L, Fischer C, Higgs DR (2002) Clinical phenotypes and molecular characterization of Hb H-Paksé disease. Haematologica 87:117–125
Wasi P, Pootrakul S, Pootrakul P, Pravatmuang P, Winichagoon P, Fucharoen S (1980) Thalassemia in Thailand. Ann N Y Acad Sci 344:352–363.
Waye JS, Eng B, Patterson M, Chui DHK, Olivieli NF (1994) Identification of a novel termination codon mutation (TAA→TAT, Term→Tyr) in the α2-globin gene of a Laotian girl with hemoglobin H disease. Blood 83:3418–3420
Weatherall DJ, Clegg JB (2001) Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ 79:704–712
Weatherall DJ, Clegg JB (2001) The thalassemia syndromes, 4th edn. Blackwell Science, Oxford
Wong SC, Ali MAM (1982) Hemoglobin E disease: hematological, analytical, and biosynthetic studies in homozygotes and double heterozygotes for α-thalassemia. Am J Hematol 13:15–21
Acknowledgements
This work was supported by grants from the National Science and Technology for Development Agency (NSTDA) and the Khon Kaen University, Khon Kaen, Thailand. We thank Dr. Pattara Sanchaisuriya for help with the statistical analysis and Dr. Ian Thomas for helpful comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sanchaisuriya, K., Fucharoen, G., Sae-ung, N. et al. Molecular and hematologic features of hemoglobin E heterozygotes with different forms of α-thalassemia in Thailand. Ann Hematol 82, 612–616 (2003). https://doi.org/10.1007/s00277-003-0689-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-003-0689-y