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Amelioration of Sardinian beta0 thalassemia by genetic modifiers - PubMed

  • ️Thu Jan 01 2009

Amelioration of Sardinian beta0 thalassemia by genetic modifiers

Renzo Galanello et al. Blood. 2009.

Abstract

Sardinian beta-thalassemia patients all are homozygotes for the same null allele in the beta-globin gene, but the clinical manifestations are extremely variable in severity. Previous studies have shown that the coinheritance of alpha-thalassemia or the presence of genetic variants that sustain fetal hemoglobin production has a strong impact on ameliorating the clinical phenotype. Here we evaluate the contribution of variants in the BCL11A, and HBS1L-MYB genes, implicated in the regulation of fetal hemoglobin, and of alpha-thalassemia coinheritance in 50 thalassemia intermedia and 75 thalassemia major patients. We confirm that alpha-thalassemia and allele C of single nucleotide polymorphism rs-11886868 in BCL11A were selectively represented in thalassemia intermedia patients. Moreover, allele G at single nucleotide polymorphism rs9389268 in the HBS1L-MYB locus was significantly more frequent in the thalassemia intermedia patients. This trio of genetic factors can account for 75% of the variation differences in phenotype severity.

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Figures

Figure 1
Figure 1

Proportion of patients and number of ameliorating alleles in the 2 groups. The figure shows the proportion of thalassemia major and thalassemia intermedia patients carrying 0, 1, or more of the alleles considered to be responsible for the amelioration of the clinical expression of the phenotype (positive alleles). Persons carrying more than 4 positive alleles were not observed.

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