Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract

• Published in: Clinical genetics Vol. 86; no. 6; pp. 575 - 579
• Main Authors: 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., Xia, K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2014
• Subjects: Adult; Age of Onset; Aged; Asian Continental Ancestry Group - genetics; cataract; Cataract - epidemiology; Cataract - etiology; Cataract - genetics; Cataracts; Codon, Nonsense; Collagen; exome sequencing; Eye diseases; Female; Genes, Recessive; Genetic Predisposition to Disease; high myopia; Homozygote; Humans; LEPREL1; Male; Middle Aged; Mutation; Myopia - complications; Myopia - genetics; Pathogenesis; Pedigree; Procollagen-Proline Dioxygenase - genetics; exome sequencing; LEPREL1; cataract; high myopia
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.12309

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.