Communicated by Graham R. Taylor
EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients†
Article first published online: 8 FEB 2011
© 2011 Wiley-Liss, Inc.
Volume 32, Issue 3, pages 325–334, March 2011
How to Cite
Caux-Moncoutier, V., Castéra, L., Tirapo, C., Michaux, D., Rémon, M.-A., Laugé, A., Rouleau, E., De Pauw, A., Buecher, B., Gauthier-Villars, M., Viovy, J.-L., Stoppa-Lyonnet, D. and Houdayer, C. (2011), EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. Hum. Mutat., 32: 325–334. doi: 10.1002/humu.21414
- Issue published online: 22 FEB 2011
- Article first published online: 8 FEB 2011
- Accepted manuscript online: 30 NOV 2010 03:17PM EST
- Manuscript Accepted: 8 NOV 2010
- Manuscript Received: 31 JUL 2010
- Medicen and la Région Ile de France
- ANR (Agence Nationale pour la Recherche)
- capillary electrophoresis;
The detection of unknown mutations remains a serious challenge and, despite the expected benefits for the patient's health, a large number of genes are not screened on a routine basis. We present the diagnostic application of EMMA (Enhanced Mismatch Mutation Analysis®, Fluigent, Paris, France), a novel method based on heteroduplex analysis by capillary electrophoresis using innovative matrices. BRCA1 and BRCA2 were screened for point mutations and large rearrangements in 1,525 unrelated patients (372 for the validation step and 1,153 in routine diagnosis) using a single analytical condition. Seven working days were needed for complete BRCA1/2 screening in 30 patients by one technician (excluding DNA extraction and sequencing). A total of 137 mutations were found, including a BRCA2 duplication of exons 19 and 20, previously missed by Comprehensive BRACAnalysis®. The mutation detection rate was 11.9%, which is consistent with patient inclusions. This study therefore suggests that EMMA represents a valuable short-term and midterm option for many diagnostic laboratories looking for an easy, reliable, and affordable strategy, enabling fast and sensitive analysis for a large number of genes. Hum Mutat 32:1–10, 2011. © 2011 Wiley-Liss, Inc.