Estimation of the difference in HbF expression due to loss of the 5' δ-globin BCL11A binding region.
BCL11A was the focus of recent studies on its inhibiting effect when bound onto the β-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 γβ-δ intergenic region to find a possible correlation with the BCL11A binding site located 5' to the δ-globin gene. Precise characterization of deletions was achieved using a custom DNA-array chip and breakpoint sequencing. The α-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 δ-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 β-thalassemia major patients.
APHP-Molecular Genetics Department, Henri Mondor Hospital, Créteil, France.
Elyes Slim
ES
Ghedira
Laure
L
Lecerf
Emmanuelle
E
Faubert
Bruno
B
Costes
Kamran
K
Moradkhani
Dora
D
Bachir
Frédéric
F
Galactéros
Serge
S
Pissard
D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D012097:Repressor Proteins; D055815:Young Adult; D055546:delta-Globins / Q000235:genetics* / Q000378:metabolism*
C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055546:delta-Globins; D005319:Fetal Hemoglobin