None of the authors have any conflict of interests with the content of this manuscript.
Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma
Version of Record online: 27 MAY 2013
© 2013 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 84, Issue 2, pages 167–174, August 2013
How to Cite
Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma., , , , , , , , , .
- Issue online: 9 JUL 2013
- Version of Record online: 27 MAY 2013
- Accepted manuscript online: 26 APR 2013 12:01PM EST
- Manuscript Revised: 19 APR 2013
- Manuscript Accepted: 19 APR 2013
- Manuscript Received: 25 MAR 2013
- modifying gene;
Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome-wide scan for early-onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early-onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early-onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.