The genomic and epigenomic landscape of iridocorneal endothelial syndrome  

作　　者：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 

机构地区：[1]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 [2]Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou,Guangdong 510623,China [3]Eye Hospital(The Third Hospital of Handan),Handan,Hebei 056000,China [4]Department of Ophthalmology,Department of Ophthalmology&Optometry,Fujian Medical University,Fuzhou,Fujian 350004,China [5]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 [6]Department of Ophthalmology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [7]Cangzhou Aier Eye Hospital,Cangzhou,Hebei 061000,China [8]Nangchang Aier Eye Hospital,Nanchang,Jiangxi 330002,China [9]The Third Affiliated Hospital of Nanchang University,Nanchang,Jiangxi 330008,China [10]The First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China [11]Department of Ophthalmology,Yichang Central People’s Hospital,The First College of Clinical Medical Science,China Three Gorges University,Yichang,Hubei 443003,China [12]Kunming Huashan Eye Hospital,Kunming,Yunnan 650032,China [13]Kunming Aier Eye Hospital,Kunming,Yunnan 650041,China [14]Affiliated Eye Hospital of Nanchang University,Jiangxi Research Institute of Ophthalmology and Visual Science,Nanchang,Jiangxi 330006,China [15]Shenzhen Eye Hospital,Shenzhen,Guangdong 518000,China [16]Department of Ophthalmology,Xi’an Fourth Hospital,Xi’an,Shaanxi 710004,China [17]Department of Ophthalmology,Second Hospital of Hebei Medical University,Shijiazhuang,Hebei 050000,China [18]Eye Center of Xiangya Hospital,Central South University,Hunan Key Laboratory of Ophthalmology,Changsha,Hunan 410008,China [19]Department of Ophthalmolog

出　　处：《Genes & Diseases》2025年第3期523-532,共10页基因与疾病(英文)

基　　金：supported by the National Key Research and Development Program of China(No.2022YFC2502800);the National Natural Science Foundation of China(No.82070955,32000537).

摘　　要：Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye diseasewith an unknown etiology. Understanding its genomic and epigenomic landscape could aid indeveloping etiology-based therapies. In this study, we recruited 99 ICE patients and performedwhole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 ofthem. We conducted mutational burden testing on genes and noncoding regulatory regions,comparing the ICE cohort with control groups (9197 East Asians from the gnomAD databaseand 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysisand 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 regionswith 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 methylationcompared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.

关 键 词：Copy number variance DNA methylation ETIOLOGY Iridocorneal endothelial syndrome Whole-genome sequencing 

分 类 号：R73[医药卫生—肿瘤]