The British type of non‐deletion HPFH: characterization of developmental changes in vivo and erythroid growth in vitro

Publisher Website
Google Scholar
Abstract
Further studies of a unique British family with a rare type of hereditary presistence of fetal Hb (HPFH) confirmed that this condition results from a regulatory defect affectiing globin gene expression. Adult heterozygotes for this disorder have 3.5-10.0% Hb F, while homozygotes have 18-21% Hb F; in both cases the Hb F contained predominantly A.gamma. chains (89-94%). In all other respects these individuals were hematologically normal. Two obligate heterozygotes were studied from birth, at which time both the proportion of Hb F and the G.gamma./A.gamma. ratio were completely normal. There was a delayed decline in Hb F which continued well into childhood and a parallel decline in the proportion of G.gamma. chains. The growth of erythroid bursts showed no difference in number, size or erythropoietin responsiveness between homozygous HPFH, heterozygous HPFH or normal family members. Hb synthesis in these bursts showed the normal pattern of asynchrony between .gamma. and .beta. chain synthesis, but there was an overall increase in .gamma. chain production in the HPFH cases, particularly the homozygotes, compared to normal. The abnormal G.gamma./A.gamma. ratio was faithfully reproduced in vitro. This condition appears to result from a regulatory abnormality affecting the postnatal repression of .gamma. chain synthesis.