Communicated by Mario Tosi
Usher syndrome type 2 caused by activation of an USH2A pseudoexon: Implications for diagnosis and therapy†
Article first published online: 16 NOV 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 1, pages 104–108, January 2012
How to Cite
Vaché, C., Besnard, T., le Berre, P., García-García, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M. and Roux, A.-F. (2012), Usher syndrome type 2 caused by activation of an USH2A pseudoexon: Implications for diagnosis and therapy. Hum. Mutat., 33: 104–108. doi: 10.1002/humu.21634
- Issue published online: 14 DEC 2011
- Article first published online: 16 NOV 2011
- Accepted manuscript online: 18 OCT 2011 03:44PM EST
- Manuscript Accepted: 7 OCT 2011
- Manuscript Received: 27 JUL 2011
- le Ministère de la Recherche “PHRC National 2004, PROM 7802.”
- Spanish Ministry of Science and Innovation (to G.G.-G.)
- Usher syndrome;
USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified a single pathogenic alteration in one of them and a different mutation in the two affected nieces. As the patients carried a common USH2A haplotype, they likely shared a mutation not found by standard sequencing techniques. Analysis of RNA from nasal cells in one affected individual identified an additional pseudoexon (PE) resulting from a deep intronic mutation. This was confirmed by minigene assay. This is the first example in Usher syndrome (USH) with a mutation causing activation of a PE. The finding of this alteration in eight other individuals of mixed European origin emphasizes the importance of including RNA analysis in a comprehensive diagnostic service. Finally, this mutation, which would not have been found by whole-exome sequencing, could offer, for the first time in USH, the possibility of therapeutic correction by antisense oligonucleotides (AONs). Hum Mutat 33:104–108, 2012. © 2011 Wiley Periodicals, Inc.