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 language | English (US) |
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Pages (from-to) | 270-275 |
Number of pages | 6 |
Journal | American Journal of Hematology |
Volume | 44 |
Issue number | 4 |
DOIs | |
State | Published - Dec 1993 |
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