COMPARISON OF TWO KNOWN CHROMOSOMAL REARRANGEMENTS IN THE δβ-GLOBIN COMPLEX WITH IDENTICAL DNA BREAKPOINTS BUT CAUSING DIFFERENT Hb A2 LEVELS

We report three cases with very heterogeneous Hb A(2) levels caused by known chromosomal rearrangements in the beta-globin locus. These rearrangements had their breakpoints at the same region in the delta gene, leading either to the Senegalese delta(0)beta(+)-thalassemia (delta(0)beta(+)-thal) deletion or to an insertion of a delta gene, known as Anti-Lepore. One patient showed, apart from drastically increased Hb A(2) values of 17.0%, inconspicuous hematological values. He had an Anti-Lepore mutation with three copies of the d gene, thus explaining the high Hb A(2) level. Two other patients had Hb A(2) levels in the lower borderline range and increased Hb F levels. Molecular analysis showed the Senegalese delta(0)beta(+)-thal deletion. One of them presented with an additional mild beta-thal mutation leading to beta-thal intermedia. These cases illustrate that different gene rearrangements with the same breakpoints in the d gene can lead to different levels of Hb A(2) depending on the remaining number of delta genes.