Fetal hemoglobin expression in the compound heterozygous state for -117 (G-->A) Agamma HPFH and IVSII-745 (C-->G) beta+ thalassemia: a case study

• Published in: American journal of hematology Vol. 61; no. 2; pp. 139 - 143
• Main Authors: Dedoussis, G V, Sinopoulou, K, Gyparaki, M, Loutradis, A
• Format: Journal Article
• Language: English
• Published: United States 01.06.1999
• Subjects: Adult; Base Sequence - genetics; beta-Thalassemia - genetics; Female; Fetal Hemoglobin - genetics; Fetal Hemoglobin - metabolism; Globins - genetics; Haplotypes - genetics; Heterozygote; Humans; Male; Middle Aged; Phenotype; RNA Caps; RNA Splicing
• ISSN: 0361-8609

We studied a family in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. The compound heterozygote is a healthy man with 43% HbF, Ggamma/Agamma 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 beta-thal heterozygotes for the same mutation. Molecular analysis of the beta-globin genotype revealed the presence of the IVSII-745 (C-->G) beta+ RNA splice mutation in trans with the -117 G-->A Greek HPFH. The beta+ 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 Ggamma promoter, which is linked with haplotype IV. He presented 13.5% HbF with a Ggamma/Agamma 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 Ggamma/Agamma ratio 31:69.