Unstable and Thalassemic α Chain Hemoglobin Variants: A Cause of Hb H Disease and Thalassemia Intermedia

Abstract

We report an update of the α-globin gene point mutations resulting in structural modification associated with an α-thalassemia (α-thal) phenotype. These variants, barely symptomatic in the heterozygous state, are either unstable due to folding defects and/or defects in binding to α-hemoglobin stabilizing protein (AHSP). This is predicted to result in precipitation of the unstable α chains or Hb variant, a concomitant decrease in the overall quantity of normal α-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 α-thal defects are discussed.

Keywords:

• Hemoglobin (Hb)
• α-Hb stabilizing protein (AHSP)
• α-Thalassemias
• Unstable Hbs