Interaction of two different disorders in the beta-globin gene cluster associated with an increased hemoglobin F production: a novel deletion type of G gamma + (A gamma delta beta)zero-thalassemia and a delta zero-hereditary persistence of fetal hemoglobin determinant. We report two different disorders of the beta-globin gene cluster segregating in a Belgian family: a novel deletion that results in G gamma + (A gamma delta beta)zero-thalassemia (thal) and a heterocellular hereditary persistence of foetal hemoglobin of the Swiss type linked to a delta degree-thal gene (delta degree-HPFH). Heterozygosity for the heterocellular HPFH brings about a moderate (3.4% to 8.24%) increase of hemoglobin (Hb) F having a G gamma/A gamma ratio of 4:1, whereas carriers of the G gamma + (A gamma delta beta)zero-thal deletion show in their peripheral blood a considerably higher (15%) percentage of Hb F. Both defects interact in the compound heterozygotes for G gamma + (A gamma delta beta)zero-thal and delta zero-HPFH producing a further increase (up to 24%) of fetal Hb consisting entirely of G gamma chains. Molecular characterization of the G gamma + (A gamma delta beta)zero-thal by means of Southern analysis showed that the deletion spans about 50 kb, removing the 3' end of the A gamma-gene, the psi beta-, delta-, and beta-genes. A number of possible mechanisms leading to the overproduction of Hb F in HPFH and G gamma + (A gamma delta beta)zero-thal will be discussed. 