KLF1 gene mutations cause borderline HbA2

Abstract

Abstract Increased hemoglobin A2 (HbA2; ie, levels > 3.9%) is the most important feature of β-thalassemia carriers. However, it is not uncommon to find persons with borderline HbA2 (levels, 3.3%-3.8%), who pose a relevant screening problem. Several genotypes have been associated with borderline HbA2, but sometimes the reasons for this unusual phenotype are unknown. In this paper, we report, for the first time, that mutations of KLF1 result in HbA2 levels in the borderline range. Six different KLF1 mutations were identified in 52 of 145 subjects with borderline HbA2 and normal mean corpuscular volume and mean corpuscular hemoglobin. Two mutations (T327S and T280_H283del) are here reported for the first time. The prevalent mutation in Sardinians is S270X, which accounts for 80.8% of the total. The frequent discovery of KLF1 mutations in these atypical carriers may contribute significantly to the thalassemia screening programs aimed at identification of at risk couples.