Estimation of the difference in HbF expression due to loss of the 5' ?-globin BCL11A binding region.

ABSTRACT: BCL11A was the focus of recent studies on its inhibiting effect when bound onto the ?-globin cluster in the mechanism of hemoglobin switching and HbF downregulation. We examined a cohort of 10 patients displaying different HbF levels and short deletions within the ??-? intergenic region to find a possible correlation with the BCL11A binding site located 5' to the ?-globin gene. Precise characterization of deletions was achieved using a custom DNA-array chip and breakpoint sequencing. The ?-globin cluster and major SNP associated with HbF expression were genotyped. Our results show that the loss of the BCL11A binding domain located 5' to the ?-globin gene is correlated with a strong HbF difference (mean+2.7 g/dL, ratio 2.81). This result provides evidence for the use of BCL11A level down-regulation or this domain blockage for new therapies in sickle cell disease and ?-thalassemia major patients.

SUBMITTER: Ghedira ES 

PROVIDER: S-EPMC3561440 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature