Insight into genes responsible for cornea plana, megalocornea, keratoconus and brittle cornea syndrome.

IF 1.4 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2026-02-07 eCollection Date: 2026-01-01

Di Zhu, Yuxi Zheng, Yi Jiang, Dongwei Guo, Yingwei Wang, Jiamin Ouyang, Zhen Yi, Shiqiang Li, Xiaoyun Jia, Xueshan Xiao, Wenmin Sun, J Fielding Hejtmancik, Qingjiong Zhang

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引用次数: 0

Abstract

Purpose: Inherited diseases characterized by abnormal corneal morphology include cornea plana, megalocornea, keratoconus and brittle cornea syndrome. This study aims to investigate genes responsible for these diseases.

Methods: Variants in genes responsible for cornea plana, megalocornea, keratoconus and brittle cornea syndrome were analyzed and characterized by multistep bioinformatics approach based on three large data sets, including our in-house exome sequencing database from patients with inherited eye diseases, literature review, and gnomAD database. Additionally, the phenotypes of patients carrying these variants were collected.

Results: 125 variants in six genes, namely KERA (Keratocan; OMIM: 603288), CHRDL1 (Chordin-like 1; OMIM: 300350), VSX1 (Visual system homeobox 1; OMIM: 605020), TUBA3D (Tubulin, alpha-3d; OMIM: 617878), ZNF469 (Zinc finger protein 469; OMIM: 612078), and PRDM5 (PR domain-containing protein 5; OMIM: 614161), have been reported in 244 families by literature review, of which 78 with cornea plana, 38 with megalocornea, 67 with keratoconus, and 61 with brittle cornea syndrome. Three variants in KERA were identified in 2 families with cornea plana in our cohort. Moreover, all reported variants in VSX1 were reclassified as likely benign or benign based on several major evidence, including high allelic frequency in gnomAD, presence in unaffected individuals in in-house data set, and relatively tolerated by multiple computational prediction tools. Misinterpreted variants in VSX1 has been detected in up to 3.13% of the general population.

Conclusions: This study delineates the genetic and clinical landscape of cornea plana, megalocornea, keratoconus and brittle cornea syndrome for the first time. The pathogenicity of VSX1 variants could not be confirmed, making VSX1 an unlikely candidate gene for keratoconus. Correct classification of genes like VSX1 is critical in the era of genomic medicine.

本刊更多论文

洞察基因负责角膜平面，巨角膜，圆锥角膜和脆角膜综合征。

目的：以角膜形态异常为特征的遗传性疾病包括角膜平面层、大角膜、圆锥角膜和脆性角膜综合征。这项研究旨在研究导致这些疾病的基因。方法：采用多步骤生物信息学方法，基于三个大型数据集，包括我们内部的遗传性眼病患者外显子组测序数据库、文献综述和gnomAD数据库，分析和表征角膜平面、巨角膜、圆锥角膜和脆性角膜综合征相关基因的变异。此外，还收集了携带这些变异的患者的表型。结果：通过文献回顾，在244个家族中发现了KERA （Keratocan, OMIM: 603288）、CHRDL1 （chrordin样1，OMIM: 300350）、VSX1 （Visual system homeobox 1, OMIM: 605020）、TUBA3D （Tubulin, alpha-3d, OMIM: 617878）、ZNF469（锌指蛋白469，OMIM: 612078）、PRDM5 (PR结构域蛋白5，OMIM: 614161) 6个基因的125个变异，其中角膜平面78个、大角膜38个、角膜锥67个、角膜脆断综合征61个。在我们的队列中，在2个角膜平面家族中发现了KERA的3个变异。此外，根据几个主要证据，包括gnomAD的高等位基因频率，在内部数据集中未受影响的个体中存在，以及多种计算预测工具相对耐受，所有报道的VSX1变异被重新分类为可能的良性或良性。在普通人群中发现了高达3.13%的VSX1曲解变异。结论：本研究首次揭示了角膜扁平、大角膜、圆锥角膜和脆性角膜综合征的遗传学和临床特征。VSX1变异的致病性尚未得到证实，这使得VSX1不太可能是圆锥角膜的候选基因。在基因组医学时代，像VSX1这样的基因的正确分类至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.