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HbF production in β thalassaemia heterozygotes for the IVS‐II‐1 G→A β 0 ‐globin mutation. Implication of the haplotype and the G γ‐158 C→T mutation on the HbF level
Author(s) -
Dedoussis George V.Z.,
Mandilara Georgia D.,
Boussiu Marina,
Loutradis Aphrodite
Publication year - 2000
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/1096-8652(200007)64:3<151::aid-ajh2>3.0.co;2-x
Subject(s) - haplotype , fetal hemoglobin , heterozygote advantage , mutation , globin , hemoglobinopathy , compound heterozygosity , genetics , beta (programming language) , biology , microbiology and biotechnology , hemoglobin , allele , hemolytic anemia , immunology , gene , fetus , biochemistry , pregnancy , computer science , programming language
We studied the presence of the Xmn I site and the β‐globin haplotype in 24 individuals, carriers of the IVSII‐1 G→A β 0 ‐globin mutation, of whom fourteen had no detectable levels of HbF, while ten coming from 5 families, presented HbF levels ranging from 1.7 to 9% of the total Hb. Of these β‐thalassaemia heterozygotes with fetal hemoglobin, 6 were females and 4 were males with median HbF levels of 4.85% and 4% respectively, and an excess of G γ chains (range G γ/ A γ: 55/45–70/30). Of the group of carriers of β‐thalassaemia with HbF < 0.1, in all cases except one, IVSII‐1 mutation was found associated with Xmn I polymorphic site. Haplotype analysis in these individuals revealed that in 10 cases IVSII‐1 was linked with haplotype IIIb, in 1 case with haplotype IIIa, and in 3 cases with haplotype IX. On the other hand, in the group of carriers with measurable levels of HbF, IVSII‐1 was always associated with haplotype IIIa and the Xmn I site was either in‐homozygous or the heterozygous state in‐cis or in‐trans with the mutated β‐globin gene. In conclusion the results of the study of these families seem that Xmn I site in‐cis with the IVSII‐1 does not induce HbF production when this β 0 ‐thalassaemia mutation is associated with IIIb or IX haplotype. On the other hand the G γ −158 C→T mutation is associated with small amounts of HbF in IVSII‐1 heterozygotes, when the β‐globin mutation is linked to haplotype IIIa. Am. J. Hematol. 64:151–155, 2000. © 2000 Wiley‐Liss, Inc.