Molecular basis of hereditary persistence of fetal hemoglobin.
Increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia. In a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), expression of the gamma-globin gene of HbF persists at high levels in adult erythroid cells. Molecular studies of the HPFH syndromes have identified several important regulatory elements for the normal pattern of gamma-globin gene expression. Deletion as well as nondeletion types of HPFH have been identified. The nondeletion types of HPFH are characterized by the presence of point mutations, in the promoter region of one or another gamma-globin gene, that are thought to alter interactions between various transcription factors and the promoter. The deletion types of HPFH are thought to deregulate the normal developmental pattern of gamma-globin gene expression due to the juxtaposition of normally distant cis-acting factors into the vicinity of the gamma genes. These findings have provided us with a more sophisticated understanding of the molecular basis for the persistent gamma-gene expression in these syndromes and point to certain strategies for potential future attempts at gene therapy for beta-globin gene disorders.
Forget
B G
BG
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8021, USA. bernard.forget@yale.edu
D000328:Adult; D003434:Crossing Over, Genetic; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D017384:Sequence Deletion
D006455:Hemoglobins, Abnormal; C040843:hemoglobin Kenya; D005914:Globins; D005319:Fetal Hemoglobin