Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

中文翻译：

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通过全外显子组测序对 1210 个患有遗传性视网膜疾病的日本家系进行遗传表征

遗传性视网膜疾病 (IRD) 包括一组表型和遗传异质性的眼部疾病，通过进行性视网膜变性导致视力丧失。在这里，我们报告了通过日本眼遗传联盟注册并通过全外显子组测序分析的 1210 个 IRD 家系的遗传特征。最常见的表型是视网膜色素变性 (RP, 43%)，其次是黄斑营养不良/视锥细胞或视锥细胞营养不良 (MD/CORD, 13%)。总共在 37% (448/1210) 的系谱中鉴定出 67 个致病基因。第一和第二个最频繁突变的基因是EYS和RP1, 主要与常染色体隐性 (ar) RP、RP 和 arMD/CORD 相关。总体变异频率和表型变异频率的检查表明，频繁的EYS错义变异 (c.2528G>A) 具有很高的可靠性。除了 arRP 的两个已知EYS创始人突变（c.4957dupA 和 c.8805C>G）外，我们在 arMD/CORD 患者中观察到常见的RP1变异（c.5797C>T）。