Sardinian (G)γ-HPFH: A T → C substitution in a conserved 'octamer' sequence in the (G)γ-globin promoter

Abstract

A survey of hemoglobinopathies in Northern Sardinia allowed the identification of two subjects heterozygous for a new type of G(γ) hereditary persistence of fetal hemoglobin (HPFH). The G(γ)-globin gene from the HPFH chromosome showed the presence of a T → C substitution 175 nucleotides upstream of the CAP site, adding a new example of single-point mutations occurring in the promoter region of the γ-globin genes and linked to HPFH phenotypes. In this case the mutation affects the 3' end nucleotide of a conserved octamer sequence known to be present in other regulatory elements of several genes.