Mutation analysis in 129 genes associated with other forms of retinal dystrophy

157 families with retinitis pigmentosa based on exome sequencing

By Yan Xu, Liping Guan, Xueshan Xiao, Jianguo Zhang, Shiqiang Li, Hui Jiang, Xiaoyun Jia, Jianhua Yang, Xiangming Guo, Ye Yin, Jun Wang, and Qingjiong Zhang


Purpose

Mutations in 60 known genes were previously identified by exome sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study analyzed variants in 129 genes associated with other forms of hereditary retinal dystrophy in the same cohort.


Introduction

Retinitis pigmentosa (RP, OMIM 268000) is the most common and highly heterogeneous genetic group of hereditary retinal degeneration diseases, affecting one in about 3,500–5,000 individuals worldwide [1-3]. So far, mutations in over 60 genes have been reported to be responsible for about half of nonsyndromic RP [4-6]. Phenotypic and molecular genetic overlap has been observed in different forms of retinal degeneration [7,8]; for example, RP might be the main sign of syndromic RP or other related diseases [9-11]. Mutations in a few genes have been shown to cause different forms of retinal dystrophy [7], while a few genes originally held responsible for other forms of retinal dystrophy have been found to cause RP as well [12]. Systematic analysis of all genes responsible for other forms of retinal dystrophy in patients with RP is limited, especially in Chinese cohorts [13,14]. Therefore, systemic evaluation of the frequency of mutations in all genes responsible for other forms of retinal dystrophy, apart from known RP genes, would be valuable.


Our previous whole exome sequencing study detected potential pathogenic mutations in 73 known genes in 86 of 157 patients with RP [15-17]. Due to the highly heterogeneous and genetically and clinically complicated features of RP, mutations in the genes related to more severe or syndromic diseases might be ignored, and mutations in previously analyzed genes might be mistakenly used in molecular diagnosis and clinical evaluation. Therefore, it might be interested to know if mutations in genes associated with other forms of retinal dystrophy may also contribute to RP. In the present study, variants in 129 genes responsible for other forms of retinal dystrophy were analyzed based on the exome data set of the same cohort of 157 patients.


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