title: Segmental duplications involving the alpha-globin gene cluster are causing beta-thalassemia intermedia phenotypes in beta-thalassemia heterozygous patients.
abstract: We describe two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (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 alpha-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the alpha-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-alpha(3.7) triplication in trans, resulting in a total of 7 active alpha-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active alpha-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of alpha-globin genes duplication defects in cases of beta-thalassemia heterozygotes with thalassemia intermedia phenotypes.
authors.affiliation: Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: C
authors.initials: C
authors.lastname: Refaldi
authors.forename: E
authors.initials: E
authors.lastname: Cassinerio
authors.forename: M D
authors.initials: MD
authors.lastname: Cappellini
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005914:Globins