The British type of non-deletion HPFH: characterization of developmental changes in vivo and erythroid growth in vitro.
Further studies of a unique British family with a rare type of hereditary persistence of fetal haemoglobin (HPFH) have confirmed that this condition appears to result from a regulatory defect affecting globin gene expression. Adult heterozygotes for this disorder have 3.5-10.0% Hb F while homozygotes have 18-21% Hb F and in both cases the Hb F contained predominantly A gamma chains (89-94%). In all other respects these individuals were haematologically 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. Haemoglobin 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. In addition, the abnormal G gamma/A gamma ratio was faithfully reproduced in vitro. This condition appears to result, therefore, from a regulatory abnormality affecting the postnatal repression of gamma chain synthesis.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005914:Globins / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D006113:United Kingdom
D005914:Globins; D005319:Fetal Hemoglobin