A single-base change at position -175 in the 5'-flanking region of the G gamma-globin gene from a black with G gamma-beta+ HPFH

Hereditary persistence of fetal hemoglobin (HPFH) is a human hemoglobinopathy characterized by the continued expression of fetal globins during adult life. Both deletional and nondeletional forms have been described. A number of single-base changes in the immediate 5'-flanking region of the fetal G gamma and A gamma have been reported associated with nondeletional forms of HPFH. We now present the nucleotide sequence of a G gamma-globin gene from an American black with G gamma-beta + HPFH. The immediate 5'-flanking region of this G gamma gene has a T-to-C change at -175, C at -158, and a normal C at -202. Additional changes were found in IVS2 and in the immediate 3'-flanking region, some of which may represent gene-conversion events. The sequence change at -175 probably represents a second mutation associated with the G gamma-beta + HPFH phenotype in blacks. This base change alters an octamer sequence known to be of importance in the normal expression of several other genes.