Fetal hemoglobin expression in the compound heterozygous state for −117 (G→A) Aγ HPFH and IVSII‐745 (C→G) β+ thalassemia: A case study

We studied a family in which two inherited defects of the non-α-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and β-thalassemia. The compound heterozygote is a healthy man with 43% HbF, Gγ/Aγ ratio (27:73) differing from that of 10 simple heterozygotes for the Greek HPFH (92:8), normal levels of total Hb (13.3 g/dl), and reduced HbA2 levels comparing with the levels of β-thal heterozygotes for the same mutation. Molecular analysis of the β-globin genotype revealed the presence of the IVSII-745 (C→G) β+ RNA splice mutation in trans with the −117 G→A Greek HPFH. The β+ mutation was linked to haplotype VII and the Greek HPFH was associated with haplotype Ia. The father of the compound heterozygote carries the Greek HPFH in trans with the −158 C→T on the Gγ promoter, which is linked with haplotype IV. He presented 13.5% HbF with a Gγ/Aγ ratio 75:25. His daughter was a compound heterozygote for the IVSII-745 mutation in trans with the −158 C→T, while her HbF levels were 3.7% with a Gγ/Aγ ratio 31:69. Am. J. Hematol. 61:139–143, 1999. © 1999 Wiley-Liss, Inc.