Hemoglobin F production in heterocellular hereditary persistence of fetal hemoglobin and its linkage to the beta globin gene complex.

Some types of nondeletional heterocellular hereditary persistence of fetal hemoglobin (HPFH) appear to be caused by mutations in the beta globin gene cluster near the gamma globin genes, while in other cases the condition is associated with a gene or genes outside the beta globin gene complex. We have used DNA probes for chromosome 11 markers to localize the HPFH determinant in a large Australian kindred with nondeletional heterocellular HPFH. In 13 of the 58 family members studied the Hb F levels are increased to between 1.8% and 7.9%, the Hb F being composed predominantly of A gamma chains. All family members were typed for restriction fragment length polymorphisms detected by probes from the beta globin gene complex, and the nearby genetic markers D11S12, INS, and HRAS. Linkage analysis showed HPFH is closely linked to the beta globin gene cluster (confidence limits of theta, 0.0-0.19), D11S12 (theta, 0.0-0.23) and the insulin gene (theta, 0.0-0.11). These data and the gamma chain composition are consistent with HPFH in this family being caused by a mutation within the beta globin gene cluster.