Source:http://linkedlifedata.com/resource/pubmed/id/10975440
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2001-1-4
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| pubmed:abstractText |
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 (P<0.0002) compared to that in 986 simple beta-thalassemia heterozygotes with <2.5% 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 with >2.5% 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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0363-0269
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
24
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
203-20
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10975440-Chromosome Mapping,
pubmed-meshheading:10975440-Female,
pubmed-meshheading:10975440-Fetal Hemoglobin,
pubmed-meshheading:10975440-Gene Rearrangement,
pubmed-meshheading:10975440-Genotype,
pubmed-meshheading:10975440-Globins,
pubmed-meshheading:10975440-Greece,
pubmed-meshheading:10975440-Hematologic Tests,
pubmed-meshheading:10975440-Heterozygote,
pubmed-meshheading:10975440-Humans,
pubmed-meshheading:10975440-Male,
pubmed-meshheading:10975440-Point Mutation,
pubmed-meshheading:10975440-Polymorphism, Genetic,
pubmed-meshheading:10975440-Promoter Regions, Genetic,
pubmed-meshheading:10975440-beta-Thalassemia
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| pubmed:year |
2000
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| pubmed:articleTitle |
Molecular studies of beta-thalassemia heterozygotes with raised Hb F levels.
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| pubmed:affiliation |
First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Greece.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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