In hereditary persistence of fetal haemoglobin (HPFH), there is a uniformly high level of synthesis of fetal haemoglobin (Hb F: α2γ 2) in all red cells of affected adults. Other hereditary disorders of human haemoglobin synthesis may also be associated with persistent synthesis of Hb F into adult life, but usually at a lower level and in only a selected population of red cells. Previous studies in the common type of HPFH that occurs in blacks have demonstrated the presence of a total deletion of the linked β- and δ-globin genes of the adult haemoglobins Hb A (α2β2) and Hb A2 (α2δ2)1-3, including approximately 4 kilo-bases of the DNA flanking the 5′ end of the δ gene. In contrast, δβ-thalassaemia, in which Hb F synthesis is not as elevated or uniform as in HPFH, is associated with a partial deletion of the δ gene that leaves intact the 5′-flanking DNA of the gene1-5. These results provided support for previous theories6 that regulatory sequences involved in the suppression of γ-globin gene expression might be located between the γ- and δ-globin genes, and that deletion of these sequences might be responsible for the continued expression of γ-globin genes in HPFH. To extend these observations, gene mapping studies of the non-α-globin genes have now been carried out in two additional individuals wth HPFH using restriction endonuclease digestion and gel blotting of total cellular DNA according to the method of Southern16. The results indicate that the molecular defects associated with HPFH are heterogeneous even in cases with similar phenotypes such as in the common variety of HPFH that occurs in blacks.
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