Gγ-196 C→T, Aγ-201 C→T: Two novel mutations in the promoter region of the γ-globin genes associated with nondeletional hereditary persistence of fetal hemoglobin in Greece

The increased level of fetal hemoglobin in nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH) is associated with several single base substitutions in the promoter region of either the Gγ- or the Aγ-globin genes. In this study, we report two new forms of nd-HPFH found in two unrelated Greek adults with high HbF production (8.6% and 10.2% respectively) and positive for the Gγ-158 C→T substitution. Scanning by DGGE analysis and direct sequencing of the γ-globin gene 5′ promoter region revealed the presence of a Gγ-196 C→T in the first case and an Aγ-201 C→T in the second. These mutations seem to reactivate γ-genes and cause their high expression in the adult period.