Résumé
The - 158 (C -> T) nucleotide change, known as Xmn I polymorphism, occurs in (G)gamma-globin gene promoter, and results in elevated fetal hemoglobin (HbF). We found this mutation in cis of a beta(0)-thalassemia splicing mutation. Despite the complete absence of adult HbA, the phenotype was only moderately severe with no detectable alteration of alpha-globin gene expression. Interestingly, the beta-globin locus haplotype has not been described to bear the (G)gamma promoter mutation. Using a gene-specific real-time RT-PCR approach, we found a dramatic increase of both (G)gamma and (A)gamma mRNA accumulated in the reticulocytes, suggesting that the (G)gamma-promoter mutation, alone or in association with another genetic modification, alters in concert the transcription of both (G)gamma and (A)gamma. This observation is discussed in light of recent regulatory model for beta-globin locus. (C) 2010 Elsevier Inc. All rights reserved.