Unstable and thalassemic alpha chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia.

Abstract

We report an update of the alpha-globin gene point mutations resulting in structural modification associated with an alpha-thalassemia (alpha-thal) phenotype. These variants, barely symptomatic in the heterozygous state, are either unstable due to folding defects and/or defects in binding to alpha-hemoglobin stabilizing protein (AHSP). This is predicted to result in precipitation of the unstable alpha chains or Hb variant, a concomitant decrease in the overall quantity of normal alpha-globin in the red cells and a potential degree of anemia and possibly, hemolysis. Genotype/phenotype correlation and potential genetic risk in combination with common or less common alpha-thal defects are discussed.

• Authors: Henri Wajcman, Jan Traeger-Synodinos, Ioannis Papassotiriou, Piero C Giordano, Cornelis L Harteveld, Véronique Baudin-Creuza, John Old
• Journal: Hemoglobin (Hemoglobin) Vol. 32 Issue 4 Pg. 327-49 ( 2008) ISSN: 1532-432X [Electronic] England
• PMID: 18654884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Hemoglobins, Abnormal
• Globins

Topics

• Chemical Precipitation
• Genetic Variation
• Globins (chemistry, genetics)
• Hemoglobins, Abnormal (chemistry, genetics)
• Humans
• Protein Binding
• alpha-Thalassemia (genetics)