Genes and Diseases (May 2025)
The genomic and epigenomic landscape of iridocorneal endothelial syndrome
- Yaoming Liu,
- Gen Li,
- Jiaxuan Jiang,
- Sujie Fan,
- Lan Lu,
- Ting Wang,
- Guigang Li,
- Wenzong Zhou,
- Xuequn Liu,
- Yingjie Li,
- Hong Sun,
- Liang Liang,
- Yuhong Tang,
- Yang Chen,
- Jianjun Gu,
- Fei Li,
- Xiuli Fang,
- Tao Sun,
- Aiguo Lv,
- Yayi Wang,
- Peiyuan Wang,
- Tao Wen,
- Jiayu Deng,
- Yuhong Liu,
- Mingying Lai,
- Jingni Yu,
- Danyan Liu,
- Hua Wang,
- Meizhu Chen,
- Li Li,
- Xiaodan Huang,
- Jingming Shi,
- Xu Zhang,
- Kang Zhang,
- Lingyi Liang,
- Xiulan Zhang
Affiliations
- Yaoming Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Gen Li
- Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
- Jiaxuan Jiang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Sujie Fan
- Eye Hospital (The Third Hospital of Handan), Handan, Hebei 056000, China
- Lan Lu
- Department of Ophthalmology, Department of Ophthalmology & Optometry, Fujian Medical University, Fuzhou, Fujian 350004, China
- Ting Wang
- Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong 250000, China
- Guigang Li
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
- Wenzong Zhou
- Cangzhou Aier Eye Hospital, Cangzhou, Hebei 061000, China
- Xuequn Liu
- Nangchang Aier Eye Hospital, Nanchang, Jiangxi 330002, China
- Yingjie Li
- The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China
- Hong Sun
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Liang Liang
- Department of Ophthalmology, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei 443003, China
- Yuhong Tang
- Kunming Huashan Eye Hospital, Kunming, Yunnan 650032, China; Kunming Aier Eye Hospital, Kunming, Yunnan 650041, China
- Yang Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Jianjun Gu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Fei Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Xiuli Fang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Tao Sun
- Affiliated Eye Hospital of Nanchang University, Jiangxi Research Institute of Ophthalmology and Visual Science, Nanchang, Jiangxi 330006, China
- Aiguo Lv
- Eye Hospital (The Third Hospital of Handan), Handan, Hebei 056000, China
- Yayi Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Peiyuan Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Tao Wen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Jiayu Deng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Yuhong Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China
- Mingying Lai
- Shenzhen Eye Hospital, Shenzhen, Guangdong 518000, China
- Jingni Yu
- Department of Ophthalmology, Xi’an Fourth Hospital, Xi’an, Shaanxi 710004, China
- Danyan Liu
- Department of Ophthalmology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
- Hua Wang
- Eye Center of Xiangya Hospital, Central South University, Hunan Key Laboratory of Ophthalmology, Changsha, Hunan 410008, China
- Meizhu Chen
- Department of Ophthalmology, The 900th Hospital of Joint Logistic Support Force, PLA (Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University), Fuzhou, Fujian 350025, China
- Li Li
- Department of Ophthalmology, The People’s Hospital Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China
- Xiaodan Huang
- Eye Center, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
- Jingming Shi
- The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
- Xu Zhang
- Affiliated Eye Hospital of Nanchang University, Jiangxi Research Institute of Ophthalmology and Visual Science, Nanchang, Jiangxi 330006, China; Corresponding author.
- Kang Zhang
- Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China; Faculty of Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Corresponding author. Faculty of Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China.
- Lingyi Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China; Corresponding author.
- Xiulan Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, Guangdong 510060, China; Corresponding author.
- DOI
- https://doi.org/10.1016/j.gendis.2024.101448
- Journal volume & issue
-
Vol. 12,
no. 3
p. 101448
Abstract
Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye disease with an unknown etiology. Understanding its genomic and epigenomic landscape could aid in developing etiology-based therapies. In this study, we recruited 99 ICE patients and performed whole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 of them. We conducted mutational burden testing on genes and noncoding regulatory regions, comparing the ICE cohort with control groups (9197 East Asians from the gnomAD database and 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysis and differential methylation of regions were also explored. We identified RP1L1 (27/51, 53%) with a significantly higher coding-altering mutational burden in the ICE cohort (p < 8.3×10−7), with mutations predominantly at chr8:10467637 (hg19). Additionally, 41 regions with significant CNVs were identified, including two regions at chr19:15783859-15791329 (hg19) and chr3:75786061-75790887 (hg19), showing copy number loss in 39 and 19 patients, respectively. We also identified 2,717 differentially methylated regions (DMRs), with hypomethylation prevalent in ICE syndrome (91.9% of DMRs). Among these, 45 recurrent hypomethylated regions (HMRs) in more than 10% of ICE patients showed differential methylation compared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.
Keywords
- Copy number variance
- DNA methylation
- Etiology
- Iridocorneal endothelial syndrome
- Whole-genome sequencing
