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

• Published in: American journal of hematology Vol. 65; no. 3; pp. 243 - 250
• Main Authors: Lim, Sai‐Kiang, Ali, Azhar bin, Law, Hai Yang, Ng, Ivy, Chung, Maxey Chung Ming, Lee, Szu‐Hee
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.2000; Wiley-Liss
• Subjects: Anemia - complications; Anemia - genetics; Anemias. Hemoglobinopathies; beta-Thalassemia - genetics; Biological and medical sciences; Child, Preschool; Diseases of red blood cells; Globins - genetics; Hematologic and hematopoietic diseases; Humans; Male; Medical sciences; mRNA; Phenotype; Reticulocytes - chemistry; RNA, Messenger - metabolism; RT‐PCR; β‐globin; β‐thalassemia; Human; Hemoglobinopathy; Pathogenesis; Beta-Peptide chain; Exploration; Genotype; Hemopathy; Genetic disease; Case study; Globin; Phenotype; Hemolytic anemia; Messenger RNA; Gene; β-Thalassemia; Genetics
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/1096-8652(200011)65:3<243::AID-AJH12>3.0.CO;2-6

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. Am. J. Hematol. 65:243–250, 2000. © 2000 Wiley‐Liss Inc.