Molecular studies of beta-thalassemia heterozygotes with raised Hb F levels
| Autor: | Christina Vrettou, E. Kanavakis, Anna Metaxotou-Mavrommati, Ioannis Papassotiriou, J. Traeger-Synodinos, A. Stamoulakatou, Christos Kattamis, I. Basiakos, E. Maragoudaki |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Ineffective erythropoiesis
Male Heterozygote Genotype Thalassemia Clinical Biochemistry Population Biology medicine.disease_cause Compound heterozygosity Gene mapping hemic and lymphatic diseases Gene cluster medicine Humans Point Mutation education Promoter Regions Genetic Genetics (clinical) Fetal Hemoglobin Genetics Gene Rearrangement education.field_of_study Hematologic Tests Polymorphism Genetic Greece Point mutation Biochemistry (medical) beta-Thalassemia Chromosome Mapping Hematology medicine.disease Globins Female |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0363-0269 |
| Popis: | Hb F levels in beta-thalassemia heterozygotes are usually less than 2%, but amongst 1,059 patients studied, 73 (7%) had Hb F levels above 2.5% (2.6-14.0%). To investigate factors that may influence the increase of Hb F levels in these heterozygotes, we characterized the beta-thalassemia mutations and their chromosomal background, gamma-globin gene promoter variations, and alpha-globin genotypes. All 73 beta-thalassemia heterozygotes carried beta-thalassemia point mutations previously observed in the Greek population; gene mapping excluded b gene cluster deletions; only two cases had an additional gamma-globin gene (gammagammagamma/gammagamma). Five alpha-globin genes (alphaalphaalpha/alphaalpha) were detected in 17/73 cases (23%) as compared to a carrier rate of 1.76% in the general population. Molecular, hematological, and biosynthetic findings in these compound heterozygotes indicated that the raised Hb F levels were caused by cell selection due to ineffective erythropoiesis. In the remaining 56 simple beta-thalassemia heterozygotes, 11 beta-thalassemia mutations were observed, each on the expected haplotype(s), and analysis of the gamma gene promoters revealed three known polymorphisms (in linkage disequilibrium), with minimal influence on gamma-globin levels. However, the overall distribution of beta-thalassemia mutations in the 56 simple beta-thalassemia heterozygotes was significantly different (P0.0002) compared to that in 986 simple beta-thalassemia heterozygotes with2.5% Hb F, implicating an association between beta-thalassemia mutations and moderately increased Hb F levels, most notably codon 39 (C--T), IVS-II-1 (G--A), codon 6 (-A), and codon 8 (-AA), which accounted for 41/56 (73%) cases with2.5% Hb F. In the remaining 15/56 (27%) cases, no common underlying globin genotypes could explain the raised Hb F levels. Overall, this study indicates that the control of Hb F levels in beta-thalassemia heterozygotes is heterogeneous and multi-factorial. |
| Databáze: | OpenAIRE |
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