Association of unstable hemoglobin variants and heterozygous β- thalassemia: Example of a new variant HB acharnes or [β53(D4) Ala → Thr]

Abstract

We report here the functional and structural characterization of Hb Acharnes [β53(D4) Ala → Thr], an unstable and electrophoretically silent variant, that was found associated in trans with a β°-thalassemic mutation (IVSI-1 G → A), in a patient with thalassemia intermedia syndrome. This case Is discussed in comparison with other sporadic cases that we have previously investigated, resulting from the co-inheritance of a β°-thalassemic mutation (CD39 C → T) with two other types of unstable hemoglobins, Hb Koln [β98(FG5) Val → Met], and Hb Arta [β45(CD4) Phe → Cys]. It may be concluded that, in these associated forms, both the degree of instability of the variant and the altered oxygen binding properties (affecting the degree of tissue hypoxia) are major determinants of their clinical expression.