Hb adana or α259(E8)Gly→Aspβ2, A severely unstable α1‐globin variant, observed in combination with the ‐(α)20.5 KB α‐thal‐1 deletion in two Turkish patients

M. A. Çürük, A. J. Dimovski, E. Baysal, L. ‐H Gu, Ferdane Kutlar, T. P. Molchanova, B. B. Webber, Altay, A. Gürgey, T. H.J. Huisman

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57 Scopus citations

Abstract

We have identified a severely unstable hemoglobin variant through sequencing of amplified DNA involving the α1‐globin gene; the mutation is located in codon 59 (CCG CAG) andresults in a Gly—Asp replacement. This amino acid substitution concerns a glycine residue at an internal position in the E helix, which is in close contact with a glycine residue of the B helix; introduction of the larger and charged aspartic acid residue greatly affects the stability of the molecule. This variant was present in association with a common α‐thalassemia‐1 deletion [‐(α)20.5 kb] in two adults and caused a severe type of Hb H disease with anemia, low levels of Hb A2, increased → chain, and Hb Bart's. In vitro chain synthesis in reticulocytes showed a high specific activity of the variant α chain. Only a minute quantity of Hb H was present but instead about 10% of Hb Bart's was observed. The increased synthesis of γ chains was likely due to specific characteristics of a chromosome with haplotype #3, which was present in both patients. The same family was studied 18 years ago [1]; the improved methodology presently available has led to a corrected diagnosis for these patients. © 1993 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)270-275
Number of pages6
JournalAmerican Journal of Hematology
Volume44
Issue number4
DOIs
StatePublished - Jan 1 1993

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Keywords

  • Hb Bart's
  • Hb H disease
  • Unstable Hb
  • regulatory sequences
  • α ‐globin gene mutation
  • α‐thal‐1
  • ζ chain

ASJC Scopus subject areas

  • Hematology

Cite this

Çürük, M. A., Dimovski, A. J., Baysal, E., Gu, L. H., Kutlar, F., Molchanova, T. P., Webber, B. B., Altay, Gürgey, A., & Huisman, T. H. J. (1993). Hb adana or α259(E8)Gly→Aspβ2, A severely unstable α1‐globin variant, observed in combination with the ‐(α)20.5 KB α‐thal‐1 deletion in two Turkish patients. American Journal of Hematology, 44(4), 270-275. https://doi.org/10.1002/ajh.2830440410