An anemic patient with phenotypical β-thalassemic trait has elevated level of structurally normal β-globin mRNA in reticulocytes

Abstract

Of the numerous β-thalassemic mutations linked or unlinked to the β-globin gene, all invariably cause a decrease in or an absence of structurally normal β-globin mRNA when assayed. Here we report an anemic patient with an elevated α-/β globin synthesis ratio of 2.0 in his reticulocytes. The patient's blood film showed marked red cell anisopoikilocytosis, microcytosis, and hypochromia, consistent with a typical β-thalassemic trait phenotype. Acid-eluted erythrocytes contained numerous Heinz bodies. Molecular analysis of the patient's reticulocyte mRNA indicated that, compared to normal controls, there was a 3-fold elevation of β-globin mRNA when assayed by RT-PCR and a 1.5-fold elevation of β-globin mRNA when assayed by RNA slot blotting. The level of α-globin mRNA was normal when compared to that of normal adult controls. Extensive structural analysis of the β-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectively, did not detect any mutations. Tryptic mapping of purified β-globin chains also did not show any abnormal tryptic fragments. These data indicated that a relative insufficiency of structurally normal β-globin mRNA was not a cause of this β-thalassemic phenotype. Therefore, the lesion that caused this particular thalassemic phenotype is not linked to the β-globin allele. (C) 2000 Wiley-Liss,Inc.