title: Comparison of two known chromosomal rearrangements in the δβ-globin complex with identical DNA breakpoints but causing different Hb A(2) levels.
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.
authors.affiliation: IMD Institute for Medical & Molecular Diagnostics Ltd., Zürich, Switzerland. saller@imdlab.ch
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Saller
authors.forename: Kamran
authors.initials: K
authors.lastname: Moradkhani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dutly
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vinatier
authors.forename: Claude
authors.initials: C
authors.lastname: Préhu
authors.forename: Hannes
authors.initials: H
authors.lastname: Frischknecht
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
mesh_terms: D000328:Adult; D004247:DNA / Q000737:chemistry / Q000235:genetics; D053960:DNA Breaks; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics; D018628:Gene Dosage; D015321:Gene Rearrangement / Q000235:genetics*; D005838:Genotype; D006443:Hemoglobin A2 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012720:Severity of Illness Index; D017086:beta-Thalassemia / Q000235:genetics*; D055546:delta-Globins / Q000235:genetics*
chemical_list: D055546:delta-Globins; D004247:DNA; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin