Comparison of Two Known Chromosomal Rearrangements in the δβ-Globin Complex with Identical DNA Breakpoints but Causing Different Hb A₂ Levels

Abstract

We report three cases with very heterogeneous Hb A₂ levels caused by known chromosomal rearrangements in the β-globin locus. These rearrangements had their breakpoints at the same region in the δ gene, leading either to the Senegalese δ⁰β⁺-thalassemia (δ⁰β⁺-thal) deletion or to an insertion of a δ gene, known as Anti-Lepore. One patient showed, apart from drastically increased Hb A₂ values of 17.0%, inconspicuous hematological values. He had an Anti-Lepore mutation with three copies of the δ gene, thus explaining the high Hb A₂ level. Two other patients had Hb A₂ levels in the lower borderline range and increased Hb F levels. Molecular analysis showed the Senegalese δ⁰β⁺-thal deletion. One of them presented with an additional mild β-thal mutation leading to β-thal intermedia. These cases illustrate that different gene rearrangements with the same breakpoints in the δ gene can lead to different levels of Hb A₂ depending on the remaining number of δ genes.

• Hemoglobin (Hb)
• Thalassemia
• Gene rearrangement
• Hb A₂ levels
• β-Globin gene cluster