Table_2_Genotype Profile of Global EYS-Associated Inherited Retinal Dystrophy and Clinical Findings in a Large Chinese Cohort.XLSX

PurposeThe aim of this study was to probe the global profile of the EYS-associated genotype-phenotype trait in the worldwide reported IRD cases and to build a model for predicting disease progression as a reference for clinical consultation.
MethodsThis retrospective study of 420 well-documented IRD cases with mutations in the EYS gene included 39 patients from a genotype-phenotype study of inherited retinal dystrophy (IRD) conducted at the Beijing Institute of Ophthalmology and 381 cases retrieved from global reports. All patients underwent ophthalmic evaluation. Mutations were revealed using next-generation sequencing, followed by Sanger DNA sequencing and real-time quantitative PCR analysis. Multiple regression models and statistical analysis were used to assess the genotype and phenotype characteristics and traits in this large cohort.
ResultsA total of 420 well-defined patients with 841 identified mutations in the EYS gene were successfully obtained. The most common pathogenic variant was a frameshift c.4957dupA (p.S1653Kfs∗2) in exon 26, with an allele frequency of 12.7% (107/841), followed by c.8805C > A (p.Y2935X) in exon 43, with an allele frequency of 5.9% (50/841). Two new hot spots were identified in the Chinese cohort, c.1750G > T (p.E584X) and c.7492G > C (p.A2498P). Several EYS mutation types were identified, with CNV being relatively common. The mean age of onset was 20.54 ± 11.33 (4–46) years. Clinical examinations revealed a typical progression of RPE atrophy from the peripheral area to the macula.
ConclusionThis large global cohort of 420 IRD cases, with 262 distinct variants, identified genotype-phenotype correlations and mutation spectra with hotspots in the EYS gene.

研究目的：本研究旨在探究全球已报道的遗传性视网膜营养不良（IRD, Inherited Retinal Dystrophy）病例中与EYS基因相关的基因型-表型特征全貌，并构建疾病进展预测模型，为临床诊疗提供参考依据。
研究方法：本回顾性研究共纳入420例记录完整的EYS基因突变阳性IRD病例，其中39例来自北京眼科研究所开展的遗传性视网膜营养不良基因型-表型研究队列，剩余381例检索自全球已发表文献报道。所有受试者均接受眼科检查。基因突变检测采用二代测序技术，后续通过Sanger DNA测序及实时定量聚合酶链反应（real-time quantitative PCR, qPCR）验证。本研究采用多元回归模型及统计学分析方法，对该大型队列的基因型与表型特征进行评估。
研究结果：本研究最终纳入420例确诊病例，共检出841个EYS基因致病性突变。最常见的致病突变为外显子26上的移码突变c.4957dupA（p.S1653Kfs*2），等位基因频率为12.7%（107/841）；其次为外显子43上的c.8805C>A（p.Y2935X）突变，等位基因频率为5.9%（50/841）。中国队列中还发现了两个新的突变热点：c.1750G>T（p.E584X）与c.7492G>C（p.A2498P）。本研究检出多种EYS基因突变类型，其中拷贝数变异（CNV, Copy Number Variation）较为常见。受试者的平均发病年龄为20.54±11.33岁（范围4~46岁）。临床检查显示，视网膜色素上皮（RPE, Retinal Pigment Epithelium）萎缩呈现典型的从周边区域向黄斑区进展的病程特征。
研究结论：本研究纳入的420例全球IRD病例队列（共涵盖262个不同突变位点），明确了EYS基因的基因型-表型关联特征及携带突变热点的突变频谱。