The triplicated α-globin gene locus in β-thalassaemia heterozygotes: clinical, haematological, biosynthetic and molecular studies
| Autor: | Christina Vrettou, A. Metaxotou-Mavromati, J. Traeger-Synodinos, Christos Kattamis, Th. Michael, E. Maragoudaki, Emmanuel Kanavakis |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Hemolytic anemia Heterozygote congenital hereditary and neonatal diseases and abnormalities Genotype Locus (genetics) Biology hemic and lymphatic diseases Fetal hemoglobin medicine Humans Globin Child Gene Homozygote beta-Thalassemia Heterozygote advantage Hematology medicine.disease Molecular biology Globins Pedigree Hemoglobinopathy Child Preschool Multigene Family Mutation Female |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0007-1048 |
| DOI: | 10.1046/j.1365-2141.1996.d01-1939.x |
| Popis: | Excess alpha-globin chains play a major role in the pathophysiology of homozygous beta-thalassaemia. In beta-thalassaemia carriers a minor effect of alpha-globin chain excess is reflected in a minimal or mild anaemia without clinical symptoms. Factors that increase alpha-chain excess in heterozygotes are expected to accentuate the severity of the clinical and haematological phenotype. We report the clinical, haematological, biosynthetic and molecular data in three beta-thalassaemia heterozygotes with the rare interaction of homozygosity for alpha-globin gene triplication, and in 17 heterozygotes with a single additional alpha-globin gene. The three patients homozygous for the alpha-globin gene locus (anti 3.7 kb arrangement) had beta(0)-thalassaemia mutations and a diagnosis of thalassaemia intermedia, preserving haemoglobin levels around 7-8 g/dl. Of the 17 beta-thalassaemia heterozygotes (six children and 11 adults), 16 had severe beta-thalassaemia mutations interacting with an additional alpha-globin gene (13 with alpha alpha alpha anti-3.7 and four with alpha alpha alpha anti-4.2). Compared to simple beta-thalassaemia heterozygotes, they had lower haemoglobin levels and red cell indices, but higher alpha/beta biosynthesis, HbF levels and reticulocytes. Our results suggest that homozygous alpha-gene triplication interacts with a severe beta-thalassaemia mutation to cause an alpha-chain excess equivalent to that observed in homozygous beta-thalassaemia intermedia. In heterozygotes for severe beta-thalassaemia mutations with one additional alpha-globin gene, the alpha-chain excess causes a more pronounced degree of anaemia than is usually seen in simple beta-thalassaemia heterozygotes. |
| Databáze: | OpenAIRE |
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