Frequent mutations of genes involved in OXPHOS and optic neuropathy detected by whole exome sequencing of 257 Glaucoma Patients

Abstract

Purpose : Glaucoma is a common disease with characteristic optic neurodegeneration and associated visual dysfunction. Mitochondrial oxidative phosphorylation (OXPHOS) system play critical roles in human neurodegenerative diseases. Mutations of several genes involved in OXPHOS or optic neuropathy have been identified in patients with glaucoma. This study aims to evaluate systemically mutations of genes involved in OXPHOS and optic neuropathy in a cohort of glaucoma patients.

Methods : Information of genes involved in OXPHOS and optic neuropathy were obtained based on Pubmed and google scholar research. Variants in 192 genes from 257 Chinese patients with primary glaucoma were selected from our previous whole exome sequencing data. The variants were filtered through multi-step bioinformatics analysis.

Results : A total of 90 rare functional mutations in 35 of the 192 genes were detected in 87 of 257 patients with glaucoma. The mutation frequency of these genes were significantly different between patients with glaucoma and subjects enrolled in Exome Aggregation Consortium (P<0.001). The most frequent mutant genes were DMPK (14, 5.4%), FGFR2 (7, 2.7%), DNMT1 (6, 2.3%), and PLA2G6 (5, 1.9%). Analysis of the association between these mutations and phenotype is on the way.

Conclusions : The high mutation frequency of genes associated with OXPHOS and optic neuropathy in patients with glaucoma suggests that mutational pressure in these genes might be common risk factors for glaucoma. These novel findings need be validated in different ethnic groups.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.