Globin gene expression in hereditary persistence of fetal haemoglobin and (delta beta) (0)-thalassaemia.
Recent advances in molecular and cell biology have led to major insights into understanding the regulation of globin gene expression in erythroid cells. Studies on HPFH and related syndromes have contributed much to this knowledge. Although no single explanation has emerged concerning the mechanism by which the deletional HPFH and (delta beta)(0)-thalassaemia affect HbF expression, they have led to new testable hypotheses to explain how different deletions result in similar phenotypes. The non-deletional HPFH and related syndromes have been the subject of recent intense interest, and a number of these disorders are now known to be associated with single-base changes in the promoter regions of one or the other fetal globin genes. If these base changes are causally related to the observed phenotypes, the molecular basis by which they increase HbF and simultaneously decrease HbA production remains to be determined. In addition, it has been recognized that other single-base changes 5' to the fetal-globin genes are associated with and may affect the phenotypic expression of certain forms of sickle-cell disease and beta-thalassaemia. Increased HbF production and high G gamma: A gamma ratios result in these individuals only under conditions of erythropoietic stress. The relationship between these point mutations and the cell biology of erythroid development clearly needs to be better delineated. Studies on HbF expression in humans will no doubt lead to elucidation of the mechanisms controlling the regulated expression of globin gene switching in normal and disease states, and hopefully, result in the design of molecular strategies for the amelioration of many of the human haemoglobinopathies.
Poncz
M
M
Henthorn
P
P
Stoeckert
C
C
Surrey
S
S
D000818:Animals; D001483:Base Sequence; D004912:Erythrocytes / Q000166:cytology; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D005914:Globins / Q000172:deficiency; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013577:Syndrome; D013789:Thalassemia / Q000235:genetics*
D005914:Globins; D005319:Fetal Hemoglobin