Fetal hemoglobin expression in the compound heterozygous state for -117 (G-->A) Agamma HPFH and IVSII-745 (C-->G) beta+ thalassemia: a case study.
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.
Dedoussis
G V
GV
LAIKO General Hospital, Center for Thalassemia, Athens, Greece. dedousi@hua.gr
Sinopoulou
K
K
Gyparaki
M
M
Loutradis
A
A
D000328:Adult; D001483:Base Sequence / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism*; D005914:Globins / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012315:RNA Caps; D012326:RNA Splicing; D017086:beta-Thalassemia / Q000235:genetics*
D012315:RNA Caps; D005914:Globins; D005319:Fetal Hemoglobin