Hb E (α<sub>2</sub>β<sub>2</sub><sup>26 glu→lys</sup>) is one of tne most common haemoglobin variants, found in an estimated 30 million people in South-East Asia. Homozygotes for Hb E are only mildly anaemic but compound heterozygotes with β thalassaemia have a severe clinical disorder which is the commonest form of symptomatic thalassaemia in S.E. Asia. The reasons for the high frequency of the S E gene and the severity of its interaction with β thalassaemia have never been adequately explained. We have studied eight Hb E homozygotes and nine heterozygotes all of S.E. Asian origin. In peripheral blood reticulocytes of homozygotes there was marked deficit of β<sup>E</sup> chain synthesis relative to α chain synthesis (α/β<sup>E</sup> ratio 2.0-3.3) and this was also observed to a lesser degree in the heterozygotes (1.23-2.19). There was no evidence that this was due to rapid destruction of the newly synthesised β<sup>E</sup> chains, nor that Hb E was preferentially destroyed during the lifespan of the red cell. Measurement of the ratios of α/β globin mRNA in the reticulocytes of these subjects showed E a deficit of 3 mRNA consistent with the decreased β<sup>E</sup> chain synthesis in these cells. Assessment of α/β mRNA ratios in bone marrow samples suggested normal transcription of β<sup>E</sup> mRNA and transport out of the nucleus but that once in the cytoplasm the β<sup>E</sup> mRNA was relatively unstable. The nature of the mRNA defect is unknown and could result either from the base substitution responsible for the amino acid change or from a second independent mutation in this gene. Thus the β<sup>E</sup> gene acts as a mild β thalassaemia gene, the defect acting at a pretranslational level. This explains why on interaction with β thalassaemia there is marked deficit of β chain production leading to a disorder of clinical importance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:330392 |
| Date | January 1981 |
| Creators | Synodinos, Joanne |
| Contributors | Wood, W. G. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:aa55d0fa-9196-4748-97e5-a223564f3867 |
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