Abstract
The increase of Hb A2 (α2δ2) beyond the upper limit [2.0–2.2/3.3–3.4% of the total hemoglobin (Hb)] is an invaluable tool in the hematological screening of β-thalassemia (β-thal) carriers. Factors decreasing Hb A2 percentages can hinder correct diagnosis. In order to analyze the genotype-phenotype relationship, we characterized δ-, β- and α-globin genotypes in 190 families where the probands had Hb A2 values of ≤2.0% or were β-thal heterozygotes with normal Hb A2 levels. Hb A2 was measured with cation exchange high performance liquid chromatography (HPLC). Mutations were detected with allele-specific methods or DNA sequencing; two multiplex-ARMS (amplification refractory mutation system) assays were set up. The molecular basis underlying the decrease in Hb A2 was extremely heterogeneous. Nineteen δ-globin alleles (Hb A2-S.N. Garganico was new) were detected; their interaction with α- or β-globin alleles (10 and eight, respectively) led us to observe 52 genotypes in 261 carriers. The type of δ-globin mutations, the relative genotypes, the interaction with α0-thal traits, are the most important factors in decreasing the Hb A2 percentage. These results are extremely useful in addressing the molecular diagnosis of hemoglobinopathies and thalassemias.
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