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-globin gene, all invariably cause a decrease in or an absence of structurally normal beta-globin mRNA when assayed. Here we report an anemic patient with an elevated alpha-/beta 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 beta-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 beta-globin mRNA when assayed by RT-PCR and a 1.5-fold elevation of beta-globin mRNA when assayed by RNA slot blotting. The level of alpha-globin mRNA was normal when compared to that of normal adult controls. Extensive structural analysis of the beta-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectively, did not detect any mutations. Tryptic mapping of purified beta-globin chains also did not show any abnormal tryptic fragments. These data indicated that a relative insufficiency of structurally normal beta-globin mRNA was not a cause of this beta-thalassemic phenotype. Therefore, the lesion that caused this particular thalassemic phenotype is not linked to the beta-globin allele.
Lim
S K
SK
National University Medical Institutes, The National University of Singapore, Singapore. nmilimsk@nus.edu.sg
Ali
A
A
Law
H Y
HY
Ng
I
I
Ming Chung
M C
MC
Lee
S H
SH
D000740:Anemia / Q000150:complications* / Q000235:genetics*; D002675:Child, Preschool; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000737:chemistry*; D017086:beta-Thalassemia / Q000235:genetics*
D012333:RNA, Messenger; D005914:Globins