The genomic and epigenomic landscape of iridocorneal endothelial syndrome

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<sup>-7</sup>), 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.

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Publication Details

Journal
Genes & Diseases
Published
2024-11-07
DOI
https://doi.org/10.1016/j.gendis.2024.101448
Primary Topic
Renal and Vascular Pathologies
Type
article
Field-Weighted Citation Impact
0.00

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article

The genomic and epigenomic landscape of iridocorneal endothelial syndrome

Xiaodan Huang, Danyan Liu, Yaoming Liu, Jianjun Gu et al.
Genes & Diseases
Renal and Vascular Pathologies
article

The genomic and epigenomic landscape of iridocorneal endothelial syndrome

Xiaodan Huang, Danyan Liu, Yaoming Liu, Jianjun Gu, Aiguo Lv, Xiulan Zhang, Guigang Li, Meizhu Chen, Xuequn Liu, Jiaxuan Jiang, Chen Yang, Yuhong Tang, Yayi Wang, Gen Li, Li Li, Hua Wang, Yingjie Li, Liang Liang, Ting Wang, Kang Zhang, Xu Zhang, Jinjin Li, Fei Li, Jingni Yu, Lan Lu, Jiayu Deng, Tao Wen, Tao Sun, Peiyuan Wang, Wenzong Zhou, Jingming Shi, Hong Sun, Lingyi Liang, Mingying Lai, Xiuli Fang, Sujie Fan
article en

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<sup>-7</sup>), 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.

Genes & DiseasesVol. 12(3)
Hebei Medical University (CN), Macau University of Science and Technology (MO), Fujian Medical University (CN), Central South University (CN), Nanchang University (CN), Sun Yat-sen University (CN), The Fourth People's Hospital (CN), Second Affiliated Hospital of Jiangxi University of TCM (CN), Kunming Third People's Hospital (CN), Second Hospital of Hebei Medical University (CN), Cangzhou Central Hospital (CN), ShenZhen People’s Hospital (CN), Anyang Eye Hospital (CN), Third Affiliated Hospital of Nanchang University (CN), People's Hospital of Cangzhou (CN), Third Hospital of Nanchang (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), Han Dan City Eye Hospital - The Third Hospital of Handan (CN), Yichang Central People's Hospital (CN), Jiangsu Province Hospital (CN), Second Xiangya Hospital of Central South University (CN), He Eye Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Shandong Eye Hospital (CN), Xiangya Hospital Central South University (CN), Tongji Hospital (CN), Shandong First Medical University (CN), Huazhong University of Science and Technology (CN), Nanjing Medical University (CN), Guangzhou Medical University (CN)
National Natural Science Foundation of China, Key Technologies Research and Development Program, National Key Research and Development Program of China
Zero hunger
Openalex Percentile: Top 64%
Renal and Vascular Pathologies
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