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

✍ Scribed by Dedoussis, George V.Z.; Sinopoulou, Klio; Gyparaki, Marilena; Loutradis, Aphroditi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 265 KB
• Volume: 61
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199906)61:2<139::aid-ajh12>3.0.co;2-7

✦ Synopsis

We studied a family in which two inherited defects of the non-␣-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and ␤-thalassemia. The compound heterozygote is a healthy man with 43% HbF, G ␥/ A ␥ 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 HbA 2 levels comparing with the levels of ␤-thal heterozygotes for the same mutation. Molecular analysis of the ␤-globin genotype revealed the presence of the IVSII-745 (C→G) ␤+ RNA splice mutation in trans with the -117 G→A Greek HPFH. The ␤+ 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 G ␥ promoter, which is linked with haplotype IV. He presented 13.5% HbF with a G ␥/ A ␥ 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 G ␥/