STRUCTURALLY DIVERSE MOLECULAR DELETIONS IN THE BETA-GLOBIN GENE-CLUSTER EXHIBIT AN IDENTICAL PHENOTYPE ON INTERACTION WITH THE BETA-S-GENE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (5) , 1245-1251
Abstract
A new deletion was characterized that increases HbF synthesis in an American black women who is doubly heterozygous for this mutation and the .beta.s-gene. The 5'' endpoint is 2.4 .+-. 0.1 kilobases (kb) upstream from the .delta.-globin gene, and the 3'' endpoint is 0.2 .+-. 0.1 kb downstream from the .beta.-globin gene; the deletion is 12 kb long. Both members of the Alu moderately repetitive DNA sequence family, normally present upstream from the .delta.-globin gene, are preserved. The patient is asymptomatic with a mild anemia and 24.8% HbF. The patient''s husband and daughter have a similar clinical syndrome, with HbF levels of 22.4 and 25.4%, respectively. Both husband and daughter are doubly heterozygous for the .beta.s-gene and the Ghana type of hereditary persistence of fetal Hb (HPFH) deletion (HPFH-2). The 5'' end of this deletion is in the .psi..beta.-gene, and its total length is > 70 kb. All 3 members of the family have normocytic red cells, of which .gtoreq. 95% are F cells as detected by immunofluorescence. Culture of the erythroid progenitors (BFU-E) from both types of these compound heterozygotes in the presence of fetal sheep serum, rich in switching factor, resulted in complete suppression of HbF synthesis. Although the newly described deletion resembles the Sicilian type of .delta..beta.-thalassemia by its size and preservation of the Alu sequences, the clinical and biological phenotype produced by its interaction with the .beta.s-gene is very similar to that of the HPFH-type deletion.