The β-thalassemias refer to that group of inherited hemoglobin disorders, which are characterized by a reduced synthesis (β(+)-thalassemia) or absence (β(0)-thalassemia) of beta globin (β-globin) chain production (1).
Here we show that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe β(E)/β(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months.
DNA sequencing of the beta globin gene confirmed a GGC to a GAC mutation at codon 29 (gly to asp) for Hb Lufkin on the patient and also revealed a beta(0) thalassemia mutation, IVS-1-1 (G to A), on both the patient and his mother.
The beta-globin gene mutations cd29 C-->T, IVS-I-2 T-->C, IVS-I-5 G-->T, cd37 G-->A and poly A Kurdish AATAAA-->AATAAG are for the first time reported in Greece, whereas cd7 GAG-->TAG is a new beta(0)-thalassemia mutation detected in an adult man from Albania residing in Greece.
The primary aim of this study was the refinement of BIA technology for use in identifying the beta o 39 mutation of the beta-globin gene, a mutation which causes a common type of beta o thalassemia.
Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus).
We identified and characterized a novel beta(0)-thalassemia mutation due to partial deletion of the 5' end beta-globin gene including the mRNA cap site and a part of exon 1.
Molecular studies of the family revealed that the proband is a compound heterozygote for two previously unreported beta zero-thalassemia alleles: a frameshift mutation (-TG) at codon 67 and a deletion of the entire beta-globin gene.
The 5' breakpoint of the deletion is located about 0.13 kb upstream from the A gamma-globin gene, whereas the 3' breakpoint is located about 66 kb downstream from the beta-globin gene, about 13 kb upstream from the breakpoint of the Chinese (A gamma delta beta)zero-thalassemia.
We report here a family with delta beta zero-thalassemia from Turkey with a complex rearrangement of the beta-globin gene cluster that involves two deletions of 11.5 kb and 1.6 kb, and an inversion of 7.6 kb.
The deletion extends from 3011 bp 5' to the mRNA cap site to an L1 repeat element downstream of the beta-globin gene and is very similar to the 12.6 kb deletion of Dutch beta zero-thalassaemia.
We report a relatively mild phenotype associated with two siblings who are compound heterozygotes for Hb S and a beta zero-thalassemia mutation due to a approximately 1.4-kb deletion of the 5' region of the beta-globin gene.
Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a beta 0-thalassaemia phenotype by premature termination of the beta-globin chain synthesis.