A novel C -> A transversion within the distal CCAAT motif of the (G)gamma-globin gene in the Algerian (G)gamma beta(+)-hereditary persistence of fetal hemoglobin

Hereditary persistence of fetal hemoglobin (HPFH) is a group of genetically heterogeneous conditions characterized by the continued expression of feta l hemoglobin in adulthood. These constitute natural models for understandin g the mechanism(s) of the hemoglobin switch. Many large deletions in the be ta-globin gene cluster and point mutations in one of the fetal globin gene promoters have been described before. In this study we describe a novel C - -> A transversion (-114) in the distal CCAAT box of the (G)gamma-globin gen e promoter associated with the (G)gamma beta(+)-HPFW phenotype in an Algeri an family. Individuals heterozygous for this mutation exhibit moderate rais e in Hb F levels (0.6-3.5 %). Much higher Hb F levels (3.8- 11.2%) are obse rved when a beta degrees-thalassemmia allele is present in trans to tie her editary persistence of fetal hemoglobin allele. This novel Algerian HPFH mu tation further stresses the importance of the distal CCAAT box in the postn atal regulation of gamma-globin gene expression.