To determine whether hemoglobin regulation is normal in diseases affecting β-globin gene expression, globin synthesis was examined in members of a family of a patient with hereditary persistence of fetal hemoglobin/β(o)-thalassemia (HPFH/β(o)-thal). The HPFH defect is the Ghanian type II, with a deletion from ψβ1 to at least 20 kb 3' to β. The β(o)-thal gene has the haplotype II restriction enzyme pattern and has the β39 nonsense mutation. Erythroid colonies from blood BFU-E were radiolabeled, and globin chains were separated by gel electrophoresis. Colonies from the β(o)-thal heterozygote had non-α/α ratios more balanced than in the reticulocytes. Gamma synthesis was 11% of non-α, which is higher than in reticulocytes, but within the range seen in normal adult colonies. Both HPFH heterozygotes produced 20%-30% γ in erythroid colonies as well as reticulocytes, although non-α/α was more balanced in the colonies. The HPFH/β(o)-thal patient produced 100% γ in reticulocytes and in colonies. (G)γ and γ-synthetic proportions were not correlated at the individual colony level in the heterozygotes, suggesting that they had 'adult' and not 'fetal' progenitor cells. The Hb expression of these adult progenitors is presumably modulated normally in vivo in β(o)-thal, but the normal decrease in HbF production does not occur in gene deletion HPFH.
ASJC Scopus subject areas
- Cell Biology