Abstract
Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, α2γ2) in the absence of eryth-ropoietic stress1. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (Gγ and Aγ) globin genes, and the presence or absence of deletions involving the β and δ genes in cis to the mutation2,3. Greek HPFH is a non-deletion variety in which heterozygotes produce 10–20% HbF, predominantly due to overproduction of the Aγ chain4–9. We have cloned a 40-kilobase (kb) region of the β-globin cluster from a Greek HPFH allele and report here that a point mutation (G→A) occurs 117 base pairs (bp) 5′ to the cap site of the Aγ-globin gene, just upstream of the distal CCA AT sequence. The corresponding region of the Gγ-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression.
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Collins, F., Metherall, J., Yamakawa, M. et al. A point mutation in the Aγ-globin gene promoter in Greek hereditary persistence of fetal haemoglobin. Nature 313, 325–326 (1985). https://doi.org/10.1038/313325a0
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DOI: https://doi.org/10.1038/313325a0
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