Researchers from Brazil identified fetal hemoglobin (HbF)-boosting haplotypes that could predict clinical outcomes in pediatric patients with sickle cell anemia (SCA), a common type of sickle cell disease (SCD).

“We found that HbF-boosting haplotypes formed by the minor alleles for the functional SNPs [single nucleotide polymorphisms] of BCL11A gene and HMIP-2 intergenic region were associated with less severe hematological parameters and reduced rate of clinical complications in pediatric patients with SCA, and these HbF-boosting haplotypes of BCL11A gene and HMIP-2 intergenic region may interact to regulate HbF levels in children with SCA,” the authors explained in the Journal of Human Genetics.

The analysis of 220 children with SCA showed that the incidence of red cell transfusion, acute chest syndrome, or infection was lower in carriers of 1 or 2 copies of the minor BCL11A haplotype than in noncarriers. Moreover, noncarriers had a higher cumulative incidence of acute splenic sequestration.

Similarly, carriers of 1 or 2 copies of the minor haplotypes of the HMIP-2 intergenic region also showed increased Hb and HbF concentrations compared with noncarriers. In addition, noncarriers showed an increased risk of transfusion, acute chest syndrome, pain crisis, and infection.

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These results suggest that these HbF-boosting haplotypes might confer some protection against certain vaso-occlusive and hemolytic complications.

Children carrying both minor haplotypes of the BCL11A gene and the HMIP-2 intergenic region had the highest mean HbF concentration among all the study groups.

On the other hand, white blood cell count, platelet count, and peripheral oxygen saturation were similar between carriers and noncarriers of both the BCL11A gene or HMIP-2 intergenic region haplotypes.

HMIP-2 corresponds to the intergenic region between the HBS1L and MYB genes.


Sales RR, Nogueira BL, Belisário AR, et al. Fetal hemoglobin-boosting haplotypes of BCL11A gene and HBS1L-MYB intergenic region in the prediction of clinical and hematological outcomes in a cohort of children with sickle cell anemia. J Hum Genet. Published online September 27, 2022. doi:10.1038/s10038-022-01079-0