Analysis of copy number variations in alpha-globin gene in the cases with combined increased levels of HbF with β thalassemia

Abstract

To detect copy number changes of α-globin gene, and analyze molecular mechanism of the impacts of fetal hemoglobin (HbF) levels for α-globin gene copy numbers loss or increase. A total of 15 cases with combined increased levels of fetal hemoglobin with β-thalassemia were collected. Firstly, three common α-thalassemia deletions were validated by Gap-PCR. Secondly, the largest deletions of the β-globin gene cluster were detected by multiplex ligation-dependent probe amplification (MLPA). Among the 15 cases, there was 1 case with duplication of the α-globin gene cluster, 3 cases of SEA heterozygote deletion of the α-globin gene, 1 cases of α 3.7 deletion heterozygote of the α-globin gene, 1 case of alpha 4.2 deletion homozygote of the α-globin gene, 1 case of deletion homozygote in the like α-globin gene. A compound heterozygous for SEA and α 3.7 of the α-globin gene was also detected. However, 7 cases showed no copy numbers loss and increase of the the α-globin gene cluster. Additional α-globin gene can produce excessive α-chain, which can aggravate imbalance for α and β-chain, and cause clinical symptoms in patients with β-thalassemia. Yet, copy number loss or mutation in α-globin gene will cause a milder clinical phenotype.