A novel silent beta-thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF

MOI, PAOLO;FAÀ V;MARINI, MARIA GIUSEPPINA;ASUNIS I;IBBA G;CAO A;ROSATELLI, MARIA CRISTINA

2004-01-01

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Abstract

The silent beta-thalassemia mutation, beta(+)-101C --> T, is the only mutation currently described in the distal beta-globin CACCC box. We present a novel mutation, a C --> G transversion, in the same position. Expression analysis in heterozygous subjects demonstrated that the mutation determines a 20% reduction in the output of the P-globin gene. DNA-protein interaction and transactivation analysis correlated the decrease in the beta-globin synthesis with the reduced binding and transactivation of EKLF to the mutant promoter. These data predict that the beta-101C --> G mutation will display a silent thalassemia phenotype similar to that of the beta-101 C --> T mutation.