Fetal hemoglobin expression in the compound heterozygous state for -117(G -> A) (A)gamma HPFH and IVS-1 nt 110(G -> A) beta(+) thalassemia: a case study

The splicing defect at IVS-I-110 is by far (43.15%) the most common beta-th alassaemia mutation in Greece. The -117 (G-->A) (A)gamma hereditary persist ence of fetal hemoglobin (Greek HPFH) is also the most frequent nondeletion al HPFH in Greece. We report a case in which these two defects co-segragate s. She is a healthy female where the total Hb is 12.3 g/dl with 51% HbF and normal HbA(2). Her (G)gamma/(A)gamma ratio is 35:65 differing from that of 10 simple heterozygotes for the Greek HPFH who have ratio of 8.92. Molecul ar analysis of the beta-globin genotype revealed the presence of the IVS-I- 110 beta(+) mutation in trans to the -117 G-->A Greek HPFH. Both mutations are linked to Ia. Her father has Greek HPFH in trans to the -158 C-->T on t he (G)gamma promoter, which is linked with haplotype III alpha. He has 13% HbF with a (G)gamma/(A)gamma ratio 32:68. Her sister is a compound heterozy gote for the IVS-I-110 mutation in trans to the -158 C-->T, with HbF levels of 3% and a (G)gamma/(A)gamma ratio 72:28.