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Defective synthesis of HbE is due to reduced levels of βE mRNA

Nature volume 288, pages 497–499 (1980)Cite this article

Abstract

Haemoglobin E (α2β226GlU→Lys) is one of the commonest haemoglobin variants. There are an estimated 30 million carriers of the βE gene in South-East Asia, where they comprise more than 50% of the population in some areas1,2; however, the reasons for this high frequency have never been adequately explained. Homozygotes for HbE may be mildly anaemic, but they do not have any clinical disability3,4. However, individuals heterozygous for both βE and β thalassaemia (HbE/β thalassaemia) have a severe clinical disorder which in some cases may approach that seen in homozygous β thalassaemia3,5,6 and which is by far the commonest form of symptomatic thalassaemia in the Indian subcontinent and South-East Asia. Haemoglobin E is the only common structural variant which interacts with β thalassaemia to produce such a severe disorder and the underlying mechanism of the interaction is not known. We have studied several homozygotes and heterozygotes for HbE and show here that the βE chain is inefficiently synthesized and produces the phenotype of a mild form of β thalassaemia; hence, when inherited together with β thalassaemia it causes a marked β-chain deficit. Furthermore, the mechanism for the defective production of βE chains seems to be a reduction of βE mRNA, a most unexpected finding in a disorder caused by a single amino acid substitution and presumably by a single nucleotide change in the DNA of the β globin gene.

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Authors and Affiliations

  1. MRC Molecular Haematology Unit and Tropical Medicine Research Unit, University of Oxford, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Joanne Traeger, W. G. Wood, J. B. Clegg & D. J. Weatherall

  2. Division of Haematology, Siriraj Hospital Bangkok, Thailand

    P. Wasi

Authors
  1. Joanne Traeger
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  2. W. G. Wood
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  3. J. B. Clegg
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  4. D. J. Weatherall
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  5. P. Wasi
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Traeger, J., Wood, W., Clegg, J. et al. Defective synthesis of HbE is due to reduced levels of βE mRNA. Nature 288, 497–499 (1980). https://doi.org/10.1038/288497a0

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