BETA-THALASSEMIA WITH EXCEPTIONALLY HIGH HEMOGLOBIN-A2 - DIFFERENTIAL EXPRESSION OF THE DELTA-GLOBIN GENE IN THE PRESENCE OF BETA-THALASSEMIA

  • 1 January 1982
    • journal article
    • research article
    • Vol. 100  (4) , 548-557
Abstract
Hb A2 levels in normal adults are rarely > 3.5%. In patients heterozygous for .beta.-thalassemia, they average .apprx. 5% but do not usually exceed 7%. A family in which 4 patients with heterozygous .beta.-thalassemia had HbA2 levels of 8.4%-11.2% were studied. Globin biosynthesis studies and restriction endonuclease mapping of the .alpha.-globin loci showed homozygous or heterozygous .alpha.-thalassemia-2 as well as .beta.-thalassemia in some family members. The .delta.- and .beta.-globin genes were examined by using the restriction enzymes EcoRI, PvuII and XbaI, which cut both within and outside the coding portions of the .delta.- and .beta.-loci. Only the expected .delta.- and .beta.-globin gene containing fragments were present, excluding a crossover event producing a fusion gene that would code for .delta.-globin, but possibly be under the regulatory influence of nucleotide sequences that control the expression of the .beta.-gene. This kindred provides evidence that in the presence of .beta.-thalassemia, expression of the .delta.-gene, beyond that commonly seen, is possible. This could be a direct result of the gene defect producing .beta.-thalassemia or be due to differences in the .delta.-globin gene linked to this .beta.-thalassemia gene. The interactions of .alpha.- and .beta.-thalassemia may alter tetramer assembly and increase HbA2 levels; this possibility seems less likely.