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 beta-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-101C-->T mutation.
|
Authors | Paolo Moi, Valeria Faà, Maria Giuseppina Marini, Isadora Asunis, Giuseppe Ibba, Antonio Cao, Maria Cristina Rosatelli |
Journal | British journal of haematology
(Br J Haematol)
Vol. 126
Issue 6
Pg. 881-4
(Sep 2004)
ISSN: 0007-1048 [Print] England |
PMID | 15352994
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- DNA-Binding Proteins
- Kruppel-Like Transcription Factors
- Transcription Factors
- erythroid Kruppel-like factor
- Globins
|
Topics |
- DNA-Binding Proteins
(metabolism)
- Female
- Gene Expression
- Globins
(biosynthesis, genetics)
- Humans
- Kruppel-Like Transcription Factors
- Mutation
- Promoter Regions, Genetic
(genetics)
- Transcription Factors
(metabolism)
- Transcriptional Activation
- beta-Thalassemia
(genetics, metabolism)
|