These authors contributed equally to this work.
Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract
Article first published online: 26 NOV 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 86, Issue 6, pages 575–579, December 2014
How to Cite
Guo, H., Tong, P., Peng, Y., Wang, T., Liu, Y., Chen, J., Li, Y., Tian, Q., Hu, Y., Zheng, Y., Xiao, L., Xiong, W., Pan, Q., Hu, Z. and Xia, K. (2014), Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract. Clinical Genetics, 86: 575–579. doi: 10.1111/cge.12309
All of the authors declare no conflict of interest.
- Issue published online: 20 NOV 2014
- Article first published online: 26 NOV 2013
- Accepted manuscript online: 30 OCT 2013 08:57AM EST
- Manuscript Accepted: 28 OCT 2013
- Manuscript Revised: 11 OCT 2013
- Manuscript Received: 23 SEP 2013
- National Basic Research Program of China. Grant Number: 2012CB517902
- National Natural Science Foundation of China. Grant Numbers: 81330027, 81161120544
- Science and Technology Project of Hunan Province, China. Grant Number: 2013RS4037
- exome sequencing;
- high myopia;
High myopia is a severe visual impairment which can increase the risk of retinal degeneration, subretinal hemorrhage, choroidal neovascularization, cataract and retinal detachment. We recruited an autosomal-recessive high myopia family, with affected subjects who also present early-onset cataract, retinal degeneration and other complications. Using targeted capturing and whole exome sequencing, we identified a homozygous non-sense mutation in the LEPREL1 gene which causes premature termination of the translation at the fifth amino acid (c.13C>T; p.Q5X), co-segregating with the phenotypes. LEPREL1 encodes a proline hydroxylase called prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The results show that LEPREL1 plays an important role in eye development and homozygous loss-of-function mutation of this gene can cause severely high myopia and early-onset cataract. Our study also strongly suggests that the disruption of collagen modification is one of the pathogenic mechanisms of high myopia and cataract.