Heterogeneity in the molecular basis of three types of hereditary persistence of fetal hemoglobin and the relative synthesis of the ^Gγ and ^Aγ types of γ chain

Restriction endonuclease analyses of DNA from one Black ^Gγ^Aγ-HPFH homozygote and four Black and one Indian ^Gγ^Aγ-HPFH heterozygotes have identified three different HPFH types which are the result of large deletions including the δ and β genes. Two of the types are comparable to those characterized previously, but the third, which is present in the Indian heterozygote, shows a distinct difference in the size of the deletion. The 5′ end point of the deletion in this type III ^Gγ^Aγ-HPFH extends 0.5-1.0 kb beyond the 5′ end point of one of the Black types of HPFH (type I). Each of the three types is associated with a distinct ratio between the ^Gγ and the ^Aγ chains, an observation supported by family data. The highest ratio is found in the heterozygote with the Indian type III ^Gγ^Aγ-HPFH, with 69.3% ^Gγ chains, while the averages for the other types were 50.7% ^Gγ (type I) and 32.3% ^Gγ (type II).