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Xiaobo Huang, Xueshan Xiao, Xiaoyun Jia, Shiqiang Li, Miaoling Li, Xiangming Guo, Xing Liu, Qingjiong Zhang; Mutation analysis of genes associated with inherited retinal dystrophies in 257 patients with glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1982.
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© ARVO (1962-2015); The Authors (2016-present)
Patients with inherited retinal dystrophies are predisposed to primary glaucoma. Rare, high penetrant mutations in genes summarized in RetNet (https://sph.uth.edu/Retnet/) are associated with different forms of retinal dystrophies. This study evaluated whether mutations in these genes are associated with primary glaucoma.
Variants in 213 genes listed in RetNet were available in whole exome sequencing data of 257 unrelated patients with primary glaucoma. Candidate variants in six of the 213 genes were selected by multi-steps bioinformatic analysis and further validated by Sanger sequencing and control analysis.
Eight potential pathogenic mutations were detected by whole exome sequencing and six were confirmed by Sanger sequencing, including c.C484T/ p.Q162* in OPA3, c.C403T/ p.R135W, c.G409A/p.V137M, and c.G628T/p.V210F in RHO, c.C2659T/p.R887* in RIMS1, and c.2755delG/p.G919fs in RPGR. Of the six, three in RHO were previously reported to be linked to retinitis pigmentosa, while the others were novel truncation mutations. None of the mutations were present in ethnicity-matched controls and most were absent in the existing human variants databases, except for a RHO hotspot mutation (c.C403T/ p.R135W), which was considered pathogenic in the 1000 Genomes. Mutations were detected in 2.3% (6/257) of patients with primary glaucoma, with a higher frequency than the prevalence of retinal dystrophies (P<0.001).
Identification of potential pathogenic mutations in genes associated with retinal dystrophies in 2.3% of patients with primary glaucoma indicates a potential role for these genes in the development of primary glaucoma. Further study is needed to confirm our findings.
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