Abstract
THE thalassaemias are a group of inherited disorders characterised by the defective production of either α (α thalassaemias) or non-α (β and δ°β° thalassaemias) globin chains of haemoglobins (Hb)1. In β thalassaemias the decreased synthesis of β-globin chains is only partially compensated by the increased production of γ chains, which probably reflects2 the massive hypertrophy of the erythron with selective survival of the clones of adult haemoglobin F-producing cells (F cells3,4). The situation is very different in other genetic disorders of the non-α gene cluster, known as δ°β° thalassaemias and Negro type of hereditary persistence of fetal haemoglobin (HPFH). In these two forms there is a genuine increase of γ-chain production, as shown by the high level of HbF found in heterozygotes. Although a clearcut distinction from both the clinical and haematological point of view cannot be traced between these two forms, the HPFH differs from the δ°β° thalassaemia in having a higher degree of γ-chain synthesis and a more homogeneous distribution of HbF within red cells. Recently, it has been possible to carry out gene analysis on DNA prepared from β°, δ°β° thalassaemic and HPFH patients. The β-globin gene is present in β° thalassaemias5–9, but in δ°β° thalassaemias and HPFH a major deletion, possibly involving both δ and β genes, has been demonstrated by hybridisation studies8,10–12. To characterise the molecular defect in these genetic disorders more precisely, we have hybridised DNA from homozygotes with HPFH, δ°β° thalassaemia and Hb Lepore disease (in which non-α-chains are a δβ fusion product13). For this we used a pure full-size cDNAβ probe and specific 5′ end and 3′ end cDNA fragments (we designate as 5′ end cDNA the portion corresponding to the 5′ end of the mRNA; the same for the 3′ end). Our results, reported here, show that in contrast to HPFH, where a complete δ and β gene deletion occurs, in δ°β° thalassaemia a 5′-end fragment of the δ gene is present.
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OTTOLENGHI, S., GIGLIONI, B., COMI, P. et al. Globin gene deletion in HPFH, δ°β° thalassaemia and Hb Lepore disease. Nature 278, 654–657 (1979). https://doi.org/10.1038/278654a0
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DOI: https://doi.org/10.1038/278654a0
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