Thalassemia and erythroid transcription factor KLF1 mutations associated with borderline hemoglobin A2 in the Thai population

Abstract

Introduction Elevated hemoglobin (Hb) A 2 is an important diagnostic marker for β-thalassemia carriers. However, diagnosis of cases with borderline Hb A 2 may be problematic. We described the molecular characteristics found in a large cohort of Thai subjects with borderline Hb A 2 . Material and methods Examination was done on 21,657 Thai subjects investigated for thalassemia at Khon Kaen University, Thailand. A total of 202 subjects with borderline Hb A 2 (3.5–4.0%) were selectively recruited and hematological parameters were recorded. DNA variants in α-, β-, δ-globin, and Krüppel-like factor 1 (KLF1) genes were examined using PCR. Results Among 202 subjects, DNA analysis identified carriers of α + -thalassemia (n = 48; 23.8%), β-thalassemia (n = 22; 10.9%) and KLF1 mutations (n = 48; 23.8%). No molecular defect was observed in the remaining 84 (41.5%) subjects. Interaction of KLF1 and α-thalassemia was observed in 10 cases. Of the 22 β-thalassemia carriers, five β + -thalassemia mutations were identified with lower MCV and higher Hb A 2 . Seven KLF1 mutations were detected in 10 genotypes in subjects with higher MCV and Hb F. No β 0 -thalassemia, α-globin gene triplication or δ-globin gene mutation was detected. Conclusions A large proportion of subjects with borderline Hb A 2 are not β-thalassemia carriers and for those with β-thalassemia, only mild β + -thalassemia mutations were detected. Evaluation of the patients using Hb A 2 , Hb F and MCV values will help in selecting cases for further molecular analysis. The results should explain the unusual phenotype of the cases and facilitate a thalassemia screening program in the region.

Keywords

• borderline hemoglobin a 2
• klf1
• thalassemia screening
• globin gene defects