Segmental duplications involving the alpha-globin gene cluster are causing beta-thalassemia intermedia phenotypes in beta-thalassemia heterozygous patients.
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.
Harteveld
C L
CL
Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
Refaldi
C
C
Cassinerio
E
E
Cappellini
M D
MD
Giordano
P C
PC
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
D005914:Globins