Fetal hemoglobin expression in the compound heterozygous state for -117 (G-->A) Agamma 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-thalassaemia mutation in Greece. The - 117 (G-->A) Agamma hereditary persistence of fetal hemoglobin (Greek HPFH) is also the most frequent nondeletional HPFH in Greece. We report a case in which these two defects co-segregates. She is a healthy female where the total Hb is 12.3 g/dl with 51% HbF and normal HbA2. Her Ggamma/Agamma ratio is 35:65 differing from that of 10 simple heterozygotes for the Greek HPFH who have ratio of 8:92. Molecular 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 the Ggamma promoter, which is linked with haplotype IIIalpha. He has 13% HbF with a Ggamma/Agamma ratio 32:68. Her sister is a compound heterozygote for the IVS-I-110 mutation in trans to the - 158 C-->T, with HbF levels of 3% and a Ggamma/Agamma ratio 72:28.
Dedoussis
G V
GV
Center for Thalassemia, Unit of Prenatal Diagnosis, LAIKO General Hospital, Athens, Greece. dedousi@hua.gr
Sinopoulou
K
K
Gyparaki
M
M
Loutradis
A
A
D000328:Adult; D001483:Base Sequence; D001609:Beta-Globulins / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006443:Hemoglobin A2 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012326:RNA Splicing; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
D001609:Beta-Globulins; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin