β°-Thalassemia in association with a γ-globin gene quadruplication

We have studied the hematology, hemoglobin composition, and globin gene arrangements in one young Turkish boy with a β°-thalassemia homozygosity and in 11 of his relatives. Evidence is presented that the chromosome with the β°-thalassemia determinant carries a γ-globin gene quadruplication, perhaps in a -(G)γ-(G)γ-(G)γ-(A)γ-gene arrangement. The eight γ-globin genes in this patients produced (G)γ and (A)γ chains in a 95 to 5 ratio, and nearly 99% of the patient's hemoglobin was of the fetal type. The clinical condition resembled that of a thalassemia intermedia. HbF levels in eight β-thalassemia heterozygotes varied between 0.5 and 4.2% and the percentages of (G)γ in this HbF averaged at 87% or 95%; this level is to some extent related to the haplotype of the normal chromosome. All subjects carried four α-globin genes; a new BglII polymorphism was observed within the ψα-globin gene.