Oligoarray comparative genomic hybridization in polycythemia vera and essential thrombo- cythemia

| 1098 | haematologica | 2008; 93(7) lower than the wild-type, which is consistent with the low circulating levels of the abnormal chain (Figure 2B). These data demonstrate that this point mutation is associated to a severe reduction of the mutant mRNA expression level, which causes a β-thalassemia phenotype by eliciting β-globin chain deficiency. The molecular mechanisms responsible for impaired gene expression have yet to be completely clarified. However, our preliminary data on mutant and normal mRNA decay rates suggest that altered RNA instability features may be involved in this process. Our study provides the first experimental evidence that a single nucleotide mutation within the coding region of the β-globin gene affects mRNA expression levels and causes a β-thalassemic defect. Furthermore, our data suggest that other regions besides the 3’UTR, whose role in constitutively regulation of this mechanism has been recently identified, may contribute to the stabilization of β-globin mRNA and could, therefore, help to characterize the molecular basis of thalassemic hemoglobinopathies.