Persistence of HbF in adults

Increased production of HbF in adults can be acquired or inherited, the latter as a primary condition or secondary to various anemias. The primary increases caused by deletions and the HBG1 or HBG2 promoter mutations are identifiable by significant increases in HbF (8 to 40 percent) in heterozygotes, and the HbF is homogeneously distributed among the red blood cells (pancellular HPFH). Common variants in Xmn1‑HBG2, HBS1L-MYB, and BCL11A contribute to the common variation in HbF persistence in adults and underlie the common HbF variation observed in all the conditions. These HbF QTL form the genetic determinants of the historically known heterocellular HPFH.