Segmental duplications involving the α-globin gene cluster are causing β-thalassemia intermedia phenotypes in β-thalassemia heterozygous patients

We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or red cell enzyme deficiencies were excluded. In one case a triplication of the α-...

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Bibliographic Details
Published in:Blood cells, molecules, & diseases molecules, & diseases, 2008-05, Vol.40 (3), p.312-316
Main Authors: Harteveld, C.L., Refaldi, C., Cassinerio, E., Cappellini, M.D., Giordano, P.C.
Format: Article
Language:English
Subjects:
16p
Adult
Alleles
beta-Thalassemia - genetics
beta-Thalassemia - physiopathology
Female
Gene Duplication
Genotype
Globins - genetics
Heterozygote
Humans
Middle Aged
MLPA
Multigene Family
Mutation
Phenotype
Polymorphism, Genetic
Thalassemia intermedia
α-globin genes
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Summary:We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or red cell enzyme deficiencies were excluded. In one case a triplication of the α-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the α-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the α-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-α 3.7 triplication in trans, resulting in a total of 7 active α-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active α-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of α-globin genes duplication defects in cases of β-thalassemia heterozygotes with thalassemia intermedia phenotypes.
ISSN:1079-9796
1096-0961
DOI:10.1016/j.bcmd.2007.11.006