Compound heterozygosity for a beta zero-thalassemia (frameshift codons 38/39; -C) and a nondeletional Swiss type of HPFH (A----C at NT -110, G gamma) in a Czechoslovakian family

Abstract

We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered beta zero-thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an A----C mutation at nucleotide -100 5' to the Cap site of G gamma), or with a compound heterozygosity for these two conditions. The Hb F level in the beta zero-thalassemia heterozygotes averaged approximately 0.3% with low G gamma values (approximately 28%) and relatively high A gamma T values (approximately 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with approximately 95% G gamma, while that of the compound heterozygote was 3.1% with approximately 95% G gamma. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%-0.2% Hb F level. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G gamma-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.