Trio-based whole-exome sequencing of 200 Chinese patients with keratoconus

Xingyong Li; Yinghao Yao; Shilai Xing; Yi-Han Zheng; Yang Zhou; Xiaoguang Yu; Jianzhong Su; Shihao Chen; Zi-Bing Jin

doi:10.1016/j.exer.2024.110109

Trio-based whole-exome sequencing of 200 Chinese patients with keratoconus

Exp Eye Res. 2024 Nov:248:110109. doi: 10.1016/j.exer.2024.110109. Epub 2024 Sep 24.

Authors

Xingyong Li¹, Yinghao Yao², Shilai Xing³, Yi-Han Zheng⁴, Yang Zhou⁵, Xiaoguang Yu³, Jianzhong Su⁶, Shihao Chen⁷, Zi-Bing Jin⁸

Affiliations

¹ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Taizhou Ophthalmology and Optometry Hospital, Taizhou, 318001, China.
² Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), The Eye Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
³ Institute of PSI Genomics, Wenzhou Global Eye & Vision Innovation Center, Wenzhou, 325024, Zhejiang, China.
⁴ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
⁵ Taizhou Ophthalmology and Optometry Hospital, Taizhou, 318001, China.
⁶ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), The Eye Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address: [email protected].
⁷ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Taizhou Ophthalmology and Optometry Hospital, Taizhou, 318001, China. Electronic address: [email protected].
⁸ Division of Ophthalmic Genetics, The Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, 100005, China.

PMID: 39326774
DOI: 10.1016/j.exer.2024.110109

Abstract

Keratoconus (KC) is a complex corneal disorder with a well-recognized genetic component. In this study, we aimed to expand the genetic spectrum of 200 Chinese patients with keratoconus and their unaffected parents. Trio-based whole-exome sequencing was performed in 200 patients with sporadic keratoconus and their unaffected parents. The variants identified in candidate genes for keratoconus were analyzed using multiple bioinformatics tools. Finally, we identified 7 variants in 5 candidate genes for keratoconus in 5 patients. The c.T464C variant in the IMPDH1 gene was defined as likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics, and the remaining variants in candidate genes (TRANK1, SLC4A11, CERKL, IFT172) were defined as uncertain significance. Our results expand the genetic spectrum in KC, highlight the genetic heterogeneity of this disease and provide important clues for future functional validation.

Keywords: Genes; Genetic heterogeneity; Keratoconus; Trio-based; Whole-exome sequencing.

MeSH terms

Adolescent
Adult
China / epidemiology
DNA Mutational Analysis
East Asian People / genetics
Exome Sequencing*
Female
Genetic Predisposition to Disease
Humans
IMP Dehydrogenase / genetics
Keratoconus* / genetics
Male
Middle Aged
Mutation
Pedigree
Young Adult

Substances

IMP Dehydrogenase