Background and Aims: A pilot screening program for thalassemia was initiated in the Lao People's Democratic Republic. This study aimed to describe the genotype diversity and hematologic features of thalassemia among the participating pregnant women. Methods: Blood samples of 411 pregnant Laotian women were collected. Hemoglobin (Hb) profiles were determined using a capillary zone electrophoresis system. Mutations of α- and β-globin genes were investigated using a polymerase chain reaction and related techniques. Results: As many as 26 different thalassemia genotypes including non-transfusion-dependent thalassemia, i.e. Hb E-β-thalassemia, Hb H, and EA Bart's diseases, were identified. A variety of phenotypic expressions of hematologic features and Hb profiles were observed, including an unusual phenotype of Hb E-β⁰ thalassemia with 89.1% Hb E, 1.6% Hb F, and 9.3% Hb A2. Conclusions: The remarkable genotype-phenotype diversity indicates a need for careful laboratory interpretation in order to provide appropriate genetic counseling and care to the Laotian population.

Keywords:
Genotype-phenotype diversity, Hemoglobinopathies, Laos, Thalassemia
1.
Weatherall DJ, Clegg JB: Inherited hemoglobin disorders: an increasing global health problem. Bull World Health Organ 2001;79:704-712.
2.
Fucharoen S, Winichagoon P: Thalassemia in Southeast Asia: problem and strategy for prevention and control. Southeast Asian J Trop Med Public Health 1992;23:47-55.
3.
Sanchaisuriya K, Fucharoen S, Ratanasiri T, Sanchaisuriya P, Fucharoen G, Dietz E, Schelp FP: Thalassemia and hemoglobinopathies rather than iron deficiency are major causes of pregnancy-related anemia in northeast Thailand. Blood Cells Mol Dis 2006;37:8-11.
4.
Tritipsombut J, Sanchaisuriya K, Phollarp P, Bouakhasith D, Sanchaisuriya P, Fucharoen G, Fucharoen S, Schelp FP: Micromapping of thalassemia and hemoglobinopathies in different regions of northeast Thailand and Vientiane, Lao People's Democratic Republic. Hemoglobin 2012;36:47-56.
5.
Savongsy O, Fucharoen S, Fucharoen G, Sanchaisuriya K, Sae-Ung N: Thalassemia and hemoglobinophathies in pregnant Lao women: carrier screening, prevalence and molecular basis. Ann Hematol 2008;87:647-654.
6.
Carnley BP, Prior JF, Gilbert A, Lim E, Devenish R, Sing H, Sarin E, Guhadasan R, Sullivan SG, Wise CA, Bittles AH, Chan K, Wong MS, Chan V, Erber WN: The prevalence and molecular basis of hemoglobinopathies in Cambodia. Hemoglobin 2006;3:463-470.
7.
Nguyen VH, Sanchaisuriya K, Wongprachum K, Duyen NM, Hoa PTT, Thang VV, Sanchaisuriya P, Fucharoen S, Schelp FP: Hemoglobin Constant Spring is markedly high in women of an ethnic minority group in Vietnam: a community-based survey and hematologic features. Blood Cells Mol Dis 2014;52:161-165.
8.
Nguyen HV, Sanchaisuriya K, Nguyen D, Phan HT, Siridamrongvattana S, Sanchaisuriya P, Fucharoen S, Fucharoen G, Schelp FP: Thalassemia and hemoglobinopathies in Thua Thien Hue, Central Vietnam. Hemoglobin 2013;37:333-342.
9.
O'Riordan S, Hien TT, Miles K, Allen A, Quyen NN, Hung NQ, Anh do Q, Tuyen LN, Khoa DB, Thai CQ, Triet DM, Phu NH, Dunstan S, Peto T, Clegg J, Farrar J, Weatherall D: Large scale screening for haemoglobin disorders in southern Vietnam: implications for avoidance and management. Br J Haematol 2010;150:359-364.
10.
Fucharoen G, Sanchaisuriya K, Sae-ung N, Dangwibul S, Fucharoen S: A simplified screening strategy for thalassaemia and haemoglobin E in rural communities in South-East Asia. Bull World Health Organ 2004;82:364-372.
11.
Yamsri S, Sanchaisuriya K, Fucharoen G, Sae-Ung N, Fucharoen S: Genotype and phenotype characterizations in a large cohort of β-thalassemia heterozygote with different forms of α-thalassemia in northeast Thailand. Blood Cells Mol Dis 2011;47:120-124.
12.
Sae-ung N, Fucharoen G, Sanchaisuriya K, Fucharoen S: α0-Thalassemia and related disorders in northeast Thailand: a molecular and hematological characterization. Acta Haematol 2007;117:78-82.
13.
Sanchaisuriya K, Fucharoen G, FucharoenS: HbPakse [(alpha2) codon 142 (TAA->TAT or Term->Tyr) J in Thai patients with EA Bart's disease and Hb H disease. Hemoglobin 2002;26:227-235.
14.
Boonsa S, Sanchaisuriya K, Fucharoen G, Wiangnon S, Jetsrisuparb A, Fucharoen S: The diverse molecular basis and hematologic features of Hb H and AEBart's diseases in northeast Thailand. Acta Haematol 2004;111:149-154.
15.
Panyasai S, Fucharoen S, Surapot S, Fucharoen G, Sanchaisuriya K: Molecular basis and hematologic characterization of deltabeta-thalassemia and hereditary persistence of fetal hemoglobin in Thailand. Haematologica 2004;89:777-781.
16.
Fucharoen S, Fucharoen G, Sanchaisuriya K, Surapot S: Molecular characterization of thalassemia intermedia associated with HPFH-6/beta-thalassemia and HPFH-6/Hb E in Thai patients. Acta Haematol 2002;108:157-161.
17.
Sanchaisuriya K, Chunpanich S, Fucharoen S, Fucharoen G, Sanchaisuriya P, Changtrakun Y: Association of Hb Q-Thailand with homozygous Hb E and heterozygous Hb Constant Spring in pregnancy. Eur J Haematol 2005;74:221-227.
18.
Weatherall DJ: The definition and epidemiology of non-transfusion dependent thalassemia. Blood Reviews 2012;26(suppl 1):S3-S6.
19.
Svasti S, Hieu TM, Munkongdee T, Winichagoon P, Van Be T, Van Binh T, Fucharoen S: Molecular analysis of beta-thalassemia in South Vietnam. Am J Hematol 2002;71:85-88.
20.
Kho SL, Chua KH, George E, Tan JA: Specific and straightforward molecular investigation of β-thalassemia mutations in the Malaysian Malays and Chinese using direct TaqMan genotyping assays. Genet Mol Res 2013;12:2409-2415.
21.
Zhang J, He J, Zeng XH, Ge SJ, Huang Y, Su J, Ding XM, Yang JQ, Cao YJ, Chen H, Zhang YH, Zhu BS: Genetic heterogeneity of the β-globin gene in various geographic populations of Yunnan in Southwestern China. PLoS One 2015;10:e0122956.
22.
Weatherall DJ, Clegg JB: The Thalassemia Syndromes, ed 4. Oxford, Blackwell Science, 2001.
23.
Olivieri NF, Muraca GM, O'Donnell A, Premawardhena A, Fisher C, Weatherall DJ: Studies in haemoglobin E beta-thalassemia. Br J Haematol 2008;141:388-397.
24.
Nuntakarn L, Fucharoen S, Fucharoen G, Sanchaisuriya K, Jetsrisuparb A, Wiangnon S: Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand. Blood Cells Mol Dis 2009;42:32-35.
25.
Nienhuis AW, Nathan DG: Pathophysiology and clinical manifestations of the β-thalassemias. Cold Spring Harb Perspect Med 2012;2:a011726.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.