Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7‐kb β‐globin gene deletion

A young woman originally from Cape Verde islands presented with mild sickle cell disease. Her blood counts and hemoglobin analysis results initially suggested that she might be either homozygous for the sickle cell hemoglobin (Hb S) with concomitant alpha-thalassemia, or compound heterozygous for Hb S and beta0-thalassemia, deletional deltabeta-thalassemia or hereditary persistence of fetal hemoglobin (HPFH). We utilized a novel polymerase chain reaction (PCR)-based screening technique and found a hitherto unrecognized 7.7-kb deletion, starting from the HBB IVSII to 3' downstream of the beta-globin gene. This diagnostic approach can be applied to decipher other similar deletional mutations. This is the second known deletion that removes the 3'-end but preserves the integrity of the 5'-end of the beta-globin gene. Furthermore, the identification of the deletion allows proper genetic counseling for affected families.