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Globin Chain Synthesis in the Greek Type (Aγ) of Hereditary Persistence of Fetal Haemoglobin

Summary. Globin chain synthesis was studied in a family with both the Greek (Aγ) type of hereditary persistence of fetal haemoglobin and β thalassaemia. The ratio of α/(γ+β+δ) chain synthesis in the hereditary persistence of fetal haemoglobin (HPFH) heterozygotes was 0.97 while in the HPFHβ‐thalassaemia heterozygote it was 2.14. However, calculation of the amounts of haemoglobin synthesized per cell suggests that in the HPFHβ‐thalassaemia heterozygote, the β‐ and Aγ‐chain genes in cis to the HPFH determinant are unable to compensate for the deficiency of chains imposed by the β‐thalassaemia gene in trans and that the increased synthesis of Hb F is directed by the y‐chain genes located on the β‐thalassaemia chromosome. The data suggest that synthesis of β and Aγ chains in the Greek HPFH is fixed at a ‘preset’ level and indicate that the defect might be due to an abnormality in the rate of transcription of the closely linked β‐, δ‐ and γ‐chain genes.