Thalassemia and erythroid transcription factor mutations associated with borderline hemoglobin A in the Thai population.

INTRODUCTION

Elevated hemoglobin (Hb) A is an important diagnostic marker for β-thalassemia carriers. However, diagnosis of cases with borderline Hb A may be problematic. We described the molecular characteristics found in a large cohort of Thai subjects with borderline Hb A.

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 (3.5-4.0%) were selectively recruited and hematological parameters were recorded. DNA variants in α-, β-, δ-globin, and Krüppel-like factor 1 () genes were examined using PCR.

RESULTS

Among 202 subjects, DNA analysis identified carriers of α-thalassemia ( = 48; 23.8%), β-thalassemia ( = 22; 10.9%) and mutations ( = 48; 23.8%). No molecular defect was observed in the remaining 84 (41.5%) subjects. Interaction of 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. Seven mutations were detected in 10 genotypes in subjects with higher MCV and Hb F. No β-thalassemia, α-globin gene triplication or δ-globin gene mutation was detected.

CONCLUSIONS

A large proportion of subjects with borderline Hb A 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, 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.