These authors contributed equally and both should be considered as first authors.
Detection of novel genetic variation in autosomal dominant retinitis pigmentosa
Article first published online: 15 APR 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Special Issue: Variant
Volume 84, Issue 5, pages 441–452, November 2013
How to Cite
Detection of novel genetic variation in autosomal dominant retinitis pigmentosa., , , , , , , .
The authors declare the absence of conflict of interest.
- Issue published online: 17 OCT 2013
- Article first published online: 15 APR 2013
- Accepted manuscript online: 27 MAR 2013 11:37AM EST
- Manuscript Revised: 22 MAR 2013
- Manuscript Accepted: 22 MAR 2013
- Manuscript Received: 8 FEB 2013
- Fondo de Investigaciones Sanitarias. Grant Numbers: PS09/01271, PI09/90754
- RIRAAF cooperative research network (RETICS). Grant Number: RD07/0064/2005
- autosomal dominant retinitis pigmentosa;
- next-generation sequencing;
- sequence capture
We explored an approach to detect disease-causing sequence variants in 448 candidate genes from five index cases of autosomal dominant retinitis pigmentosa (adRP) by sequence DNA capture and next-generation DNA sequencing (NGS). Detection of sequence variants was carried out by sequence capture NimbleGen and NGS in a SOLiD platform. After filtering out variants previously reported in genomic databases, novel potential adRP-causing variants were validated by dideoxy capillary electrophoresis (Sanger) sequencing and co-segregation in the families. A total of 55 novel sequence variants in the coding or splicing regions of adRP candidate genes were detected, 49 of which were confirmed by Sanger sequencing. Segregation of these variants in the corresponding adRP families showed three variants present in all the RP-affected members of the family. A novel mutation, p.L270R in IMPDH1, was found to be disease causing in one family. In another family a variant, p.M96T in the NRL gene was detected; this variant was previously reported as probably causing adRP. However, the previously reported p.A76V mutation in NRL as a cause of RP was excluded by co-segregation in the family. We discuss the benefits and limitations of our approach in the context of mutation detection in adRP patients.