In Sri Lanka, co-inheritance of either excess α globin genes in β thalassaemia heterozygotes or α globin gene deletions in β thalassaemia homozygotes is a significant factor in modulating disease severity.
Identification of the genetic variants modifying fetal hemoglobin (HbF) production in combination with α globin genotype provide some prediction of disease severity for β thalassemia but generation of a personalized genetic risk score to inform prognosis and guide management requires a larger panel of genetic modifiers yet to be discovered.
Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with β‑thalassemia rather than α‑globin deletions.
Xenograft assays show that a proportion of the edited CD34+ cells are long-term repopulating hematopoietic stem cells, demonstrating the potential of this approach for translation into a therapy for β-thalassemia.β-thalassemia is characterised by the presence of an excess of α-globin chains, which contribute to erythrocyte pathology.
A large body of clinical, genetic, and experimental evidence suggests that altering globin chain imbalance by reducing the production of α-globin synthesis ameliorates the disease severity in patients with β-thalassemia.
The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia.
Here we review the evidence that reduction of α-globin expression may provide an equally plausible approach to ameliorating clinically severe forms of β-thalassemia, and in particular, the very common subgroup of patients with hemoglobin E β-thalassemia that makes up approximately half of all patients born each year with severe β-thalassemia.
Our study showed that in most of the alpha thalassemia carriers just one copy of alpha globin gene was absent and they are not at risk of having children with Hb H disease or hydrops fetalis; however, up to 2.2% of neonates were carriers for ααα(anti3.7) triplication and they will be at risk for having a child with thalassemia intermediate if they marry a person which is a carrier of beta thalassemia.
Approximately 80% of α-thalassemia mutations are deletions in the α-globin cluster on chromosome 16 and about 10% of β-thalassemia mutations are deletions in the β-globin gene cluster on chromosome 11.
Our data suggest that FV vectors with the α-globin HS40 element can be used as alternative but equally efficient vehicles for human β-globin gene expression for the genetic correction of β-thalassemia.
However, the α-globin/non α-globin mRNA ratio ranged widely in β-thalassaemia/HbE patients, with no significant difference between mild and severe phenotypes.
A wide heterogeneity of the delta-globin alleles was detected; seven known alleles in trans to the beta-globin gene defects were revealed in 17 out of 18 families, while a new allele in cis to a beta-thalassemia allele was detected in one family.
In particular, HbA(2) determination plays a key role in screening programs for beta-thalassemia because a small increase in this fraction is one of the most important markers of beta-thalassemia heterozygous carriers.
Interestingly, butyrate exposure increased alpha-globin expression in beta-Thal, while alpha-globin mRNA levels decreased in SCD in response to butyrate.
Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains.
In the second case, the wife presented with a mild thalassemic picture, normal HbA(2), elevated HbF (18.5%) and a beta/alpha globin chain synthesis ratio of 0.62, without iron deficiency or any known beta-thalassemia defect, while the husband was a simple carrier of the common Mediterranean IVS-I-110 (HBB:c.93-21 G>A) mutation.
Quantification of HbA(2) in patients with and without beta-thalassemia and in the presence of HbS, HbC, HbE, and HbD Punjab hemoglobin variants: comparison of two systems.
The presence of alpha globin cluster duplication should be considered in patients heterozygote for beta-thalassemia with thalassemia intermedia phenotype and in the carriers of suspected silent beta thalassemia.