Persistence of Hb F in adults

Increased production of Hb F in adults can be acquired or inherited, the latter as a primary condition or secondary to various hereditary anemias. The primary increases caused by deletions and the HBG1 or HBG2 promoter variants are identifiable by significant increases in Hb F (to 8 to 40%) in heterozygous individuals, and the Hb F is homogeneously distributed among the red blood cells (pancellular HPFH). Common variants in the HBG2 promotor (Xmn1 site), MYB, and BCL11A contribute to the variation in Hb F persistence in adults and underlie the Hb F variation often observed in all the conditions. These are the three Hb F quantitative trait loci (QTL) that form the genetic determinants of the historically known heterocellular HPFH.