Identification and molecular characterization of four new large deletions in the β-globin gene cluster

Despite the fact that mutations in the human β-globin gene cluster are essentially point mutations, a significant number of large deletions have also been described. We present here four new large deletions in the β-globin gene cluster that have been identified on patients displaying an atypical hemoglobin phenotype (high HbF) at routine analysis. The first deletion, which spreads over 2.0 kb, removes the entire β-globin gene, including its promoter, and is associated with a typical β-thal minor phenotype. The three other deletions are larger (19.7 to 23.9 kb) and remove both the δ and β-globin genes. Phenotypically, they look like an HPFH-deletion as they are associated with normal hematological parameters. The precise localization of their 5′ and 3′ breakpoints gives new insights about the differences between HPFH and (δβ)0-thalassemia at the molecular level. The importance of detection of these deletions in prenatal diagnosis and newborn screening of hemoglobinopathies is also discussed.