A Novel Deletion of ~27 kb Including the β-Globin Gene and the Locus Control Region 3’HS-1 Regulatory Sequence: β°-Thalassemia or Hereditary Persistence of Fetal Hemoglobin?

Abstract A novel deletion of ~27 kb with the 5’ breakpoint 1.5 to 2.2 kb upstream of the β-globin gene, and the 3’ breakpoint approximately 24 kb downstream of the β-globin gene, has been found in five members of two families from Southeast Asia (Vietnam and Cambodia). Six members of another family from China, previously reported from our laboratory, have also been shown to carry this deletion. The patients presented with mild hypochromia and microcytosis, a hemoglobin (Hb) A2 level of approximately 4.0%, and a markedly increased, heterocellularly distributed, Hb F level (14.0 to 26.0%). In vitro globin-chain synthesis showed a mild imbalance with appreciable γ-chain compensation (α/β + γ ratio of 1.46). The 3’ end of this deletion includes the 3’HS-1, and we hypothesize that removal of this region results in the loss of its 7-globin gene-silencing effect, which causes a markedly elevated Hb F level with a modest increase in Hb A2 levels, unlike the situation in other deletional β°-thalassemias. The possible influence of particular sequence variations in the locus control region 5 HS-2 and the Gγ promoter, present on the chromosome with this deletion, on the overall γ-globin gene should also be considered.