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

Of the numerous beta-thalassemic mutations linked or unlinked to the beta-g lobin gene, all invariably cause a decrease in or an absence of structurall y normal beta-globin mRNA when assayed. Here we report an anemic patient wi th an elevated alpha-/beta globin synthesis ratio of 2.0 in his reticulocyt es. The patient's blood film showed marked red cell anisopoikilocytosis, mi crocytosis, and hypochromia, consistent with a typical beta-thalassemic tra it phenotype, Acid-eluted erythrocytes contained numerous Heinz bodies. Mol ecular analysis of the patient's reticulocyte mRNA indicated that, compared to normal controls, there was a 3-fold elevation of beta-globin mRNA when assayed by RT-PCR end a 3-fold elevation of beta-globin mRNA when assayed b y RNA slot blotting, The level of alpha-globin mRNA was normal when compare d to that of normal adult controls. Extensive structural analysis of the be ta-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectiv ely, did not detect any mutations. Tryptic mapping of purified beta-globin chains also did not show any abnormal tryptic fragments. These data indicat ed that a relative insufficiency of structurally normal beta-globin mRNA wa s not a cause of this beta-thalassemic phenotype. Therefore, the lesion tha t caused this particular thalassemic phenotype is not linked to the beta-gl obin allele. (C) 2000 Wiley-Liss, Inc.