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

• Published in: British journal of haematology 2004-09, Vol.126 (6), p.881-884
• Main Authors: Moi, Paolo, Faà, Valeria, Marini, Maria Giuseppina, Asunis, Isadora, Ibba, Giuseppe, Cao, Antonio, Rosatelli, Maria Cristina
• Format: Article
• Language: English
• Subjects: Anemias. Hemoglobinopathies; beta-Thalassemia - genetics; beta-Thalassemia - metabolism; Biological and medical sciences; Diseases of red blood cells; DNA-Binding Proteins - metabolism; expression studies; Female; Gene Expression; Globins - biosynthesis; Globins - genetics; Hematologic and hematopoietic diseases; Humans; Kruppel-Like Transcription Factors; Medical sciences; Mutation; Promoter Regions, Genetic - genetics; protein–DNA interaction; transcription factor; Transcription Factors - metabolism; Transcriptional Activation; β‐thalassemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.05146.x

Summary The silent β‐thalassemia mutation, β+‐101C→T, is the only mutation currently described in the distal β‐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 β‐globin gene. DNA–protein interaction and transactivation analysis correlated the decrease in the β‐globin synthesis with the reduced binding and transactivation of EKLF to the mutant promoter. These data predict that the β‐101C→G mutation will display a silent thalassemia phenotype similar to that of the β‐101C→T mutation.