A novel C→A transversion within the distal CCAAT motif of theGγ-globin gene in the algerianGγβ+-hereditary persistence of fetal hemoglobin

Abstract
Hereditary persistence of fetal hemoglobin (HPFH) is a group of genetically heterogeneous conditions characterized by the continued expression of fetal hemoglobin in adulthood. These constitute natural models for understanding the mechanism(s) of the hemoglobin switch. Many large deletions in the β-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 Gγ-globin gene promoter associated with the Gγβ+-HPFH phenotype in an Algerian family. Individuals heterozygous for this mutation exhibit moderate raise in Hb F levels (0.6-3.5 %). Much higher Hb F levels (3.8- 11.2%) are observed when a β-thalas-semia allele is present in trans to the hereditary persistence of fetal hemoglobin allele. This novel Algerian HPFH mutation further stresses the importance of the distal CCA AT box in the postnatal regulation of γ-globin gene expression.

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