Comparison of two known chromosomal rearrangements in the δβ-globin complex with identical DNA breakpoints but causing different Hb A(2) levels

Hemoglobin. 2012;36(2):177-82. doi: 10.3109/03630269.2011.644651. Epub 2012 Jan 24.

Abstract

We report three cases with very heterogeneous Hb A(2) 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 δ(0)β(+)-thalassemia (δ(0)β(+)-thal) deletion or to an insertion of a δ 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 δ 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 δ(0)β(+)-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 A(2) depending on the remaining number of δ genes.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adult
  • DNA / chemistry
  • DNA / genetics
  • DNA Breaks
  • Female
  • Fetal Hemoglobin / genetics
  • Gene Dosage*
  • Gene Rearrangement / genetics*
  • Genotype
  • Hemoglobin A2 / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Severity of Illness Index
  • beta-Thalassemia / genetics*
  • delta-Globins / genetics*

Substances

  • delta-Globins
  • DNA
  • Hemoglobin A2
  • Fetal Hemoglobin