“…First, the type of b allele (b 0 , b + or b ++ ), correlated to the amount of residual b-globin chains (Mettananda et al, 2015;Ben-Salah et al, 2017;Shang and Xu 2017;Zhong et al, 2018). Second is the co-inheritance of alpha globin locus defect, either an alpha-thalassemia deletion (a-thal) which is often observed in b-thal patients, resulting as a positive modifier or, conversely, the presence of additional copies of HBA2 or HBA1 genes which causes a more severe form of b-thal (Ben-Salah et al, 2017;Theodoridou et al, 2018;Clark et al, 2018;Harteveld et al, 2008). And third is the presence of genetic variants associated with increased fetal hemoglobin (HbF) production.…”