A novel deletion of β-globin promoter causing high HbA2 in an Indian population.

β-thalassemia is the most common inherited disorder characterized by a reduction or absence of β-globin chain synthesis. So far, over 200 mutations have been identified that result in β-thalassemia. Most of the mutations are single nucleotide substitutions or deletions, or insertions in the β-globin gene or its flanking sequences. Heterozygous β-thalassemia usually presents with mild microcytic and hypochromic anemia with a slight increase in hemoglobin A2 (HbA2) levels (3.5-5.5%). The rare large deletions in the β-globin cluster cause abnormal hemoglobin patterns in heterozygous states; deletions involving δand β-globin genes raise fetal hemoglobin (HbF) levels and those involving promoter regions of βglobin gene, without the deletion of δ-globin gene, raise HbA2 levels. Identification and characterization of these deletions are important for understanding the molecular mechanisms involved in regulation of globin genes in adults. In this study, we characterized a novel 4056bp deletion of β-globin gene and its promoter causing increased HbA2 in an Indian family. We characterized the deletion using a combination of gene dosage analysis, multiplex ligation-dependent probe amplification (MLPA) and PCR amplification across the breakpoints. The patient was a 4-year old boy born of a consan-