Xmn I polymorphism associated with concomitant activation of Gγ and Aγ globin gene transcription on a β 0-thalassemia chromosome

Abstract

The −158 (C → T) nucleotide change, known as Xmn I polymorphism, occurs in Gγ-globin gene promoter, and results in elevated fetal hemoglobin (HbF). We found this mutation in cis of a β 0-thalassemia splicing mutation. Despite the complete absence of adult HbA, the phenotype was only moderately severe with no detectable alteration of α-globin gene expression. Interestingly, the β-globin locus haplotype has not been described to bear the Gγ promoter mutation. Using a gene-specific real-time RT-PCR approach, we found a dramatic increase of both Gγ and Aγ mRNA accumulated in the reticulocytes, suggesting that the Gγ-promoter mutation, alone or in association with another genetic modification, alters in concert the transcription of both Gγ and Aγ. This observation is discussed in light of recent regulatory model for β-globin locus.