A novel silent β‐thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF
Open Access
- 16 August 2004
- journal article
- case report
- Published by Wiley in British Journal of Haematology
- Vol. 126 (6), 881-884
- https://doi.org/10.1111/j.1365-2141.2004.05146.x
Abstract
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.Keywords
This publication has 12 references indexed in Scilit:
- Cloning MafF by Recognition Site Screening with the NFE2 Tandem Repeat of HS2: Analysis of Its Role in Globin and GCSl Genes RegulationBlood Cells, Molecules, and Diseases, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Relative Quantitation of mRNA in β-Thalassemiamb E Using Real-Time Polymerase Chain ReactionHemoglobin, 2000
- A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins.Molecular and Cellular Biology, 1993
- A rapid micrqpreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cellsNucleic Acids Research, 1991
- The C–T substitution in the distal CACCC box of the β‐globin gene promoter is a common cause of silent β thalassaemia in the Italian populationBritish Journal of Haematology, 1990
- Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresisNucleic Acids Research, 1985
- Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresisNucleic Acids Research, 1981