Association of unstable hemoglobin variants and heterozygous beta-thalassemia: Example of a new variant Hb Acharnes or [beta 53(D4) Ala -> Thr]

We report here the functional and structural characterization of Hb Acharne s [beta 53(D4) Ala --> Thr], an unstable and electrophoretically silent var iant, that was found associated in trans with a beta(0)-thalassemic mutatio n (IVSI-1 G --> A), in a patient with thalassemia intermedia syndrome. This case is discussed in comparison with other sporadic cases that we have pre viously investigated, resulting from the co-inheritance of a beta(0)-thalas semic mutation (CD39 C --> T) with two other types of unstable hemoglobins, Hb Koln [beta 98(FG5) Val --> Met], and Hb Arta [beta 45(CD4) Phe --> Cys] . it may be concluded that, in these associated forms, both the degree of i nstability of the variant and the altered oxygen binding properties (affect ing the degree of tissue hypoxia) are major determinants of their clinical expression. (C) 1999 Wiley-Liss, Inc.