中国南方散发性儿童白内障患者白内障相关基因变异的检出率

IF 4.2 1区医学 Q1 OPHTHALMOLOGY

American Journal of Ophthalmology Pub Date : 2025-08-18 DOI:10.1016/j.ajo.2025.08.032

Zhengfen Luo , Shengjie Yin , Chengyao Guo , Xiaoyuan Yang , Geng Wang , Yingjie Cao , Qingping Liu , Xiaoqiang Xiao , Chi Pui Pang , Tsz Kin Ng , Mingzhi Zhang

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引用次数: 0

摘要

目的：通过全外显子组测序分析，筛选中国散发性儿童白内障患者白内障相关基因的疾病相关变异。设计：前瞻性队列研究。对象：145例散发性儿童白内障患者，来自中国南方。方法：所有患者及家长均接受完整的眼科检查。通过全外显子组测序分析和多个生物信息学程序（包括AlphaMissense和域百科全书）对495个报道的白内障相关基因的罕见变异进行了鉴定。变体通过Sanger测序进行验证，变体蛋白结构通过AlphaFold2建模。主要结果测量：从495个已报道的白内障相关基因中鉴定出疾病相关变异。结果：通过全外显子组测序，在127例患者的72个白内障相关基因中共发现155个罕见变异，而在200例不相关对照中未发现。在这些变异中，在15例患者中发现了11个先前报道的变异，在36例患者中发现了26个新的破坏性变异。在6.21%（9/145）的白内障患者中检测到CRYAA变异的频率最高。此外，儿童白内障患者存在遗传和等位基因的异质性。无义和移码变异比错义变异对alphafold2模型蛋白质结构的影响更大。结论：中国南方地区散发性白内障患者中有35.17%（51/145）存在白内障相关基因的破坏性变异，扩大了儿童白内障的遗传变异谱。

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Detection Rate of Cataract-Related Gene Variants in Sporadic Childhood Cataract Patients in Southern China

OBJECTIVE

To screen for disease-associated variants in the cataract-related genes in Chinese sporadic childhood cataract patients by whole exome sequencing analysis.

DESIGN

Prospective cohort study.

SUBJECTS

Total 145 sporadic childhood cataract patients from southern China were recruited.

METHODS

All patients and their parents received complete ophthalmic examinations. Rare variants in 495 reported cataract-related genes were identified by whole exome sequencing analysis and analyzed by multiple bioinformatics programs, including AlphaMissense and the Encyclopedia of Domains. The variants were verified by Sanger sequencing, and the variant protein structures were modeled by AlphaFold2.

MAIN OUTCOMES MEASURES

Disease-associated variants identified from 495 reported cataract-related genes.

RESULTS

In total, 155 rare variants were identified in 72 cataract-related genes in 127 patients by whole exome sequencing, which were not found in 200 unrelated control subjects. Of these variants, 11 previously reported variants were found in 15 patients, and 26 novel damaging variants were identified in 36 patients. CRYAA variants were detected with highest frequency among 6.21% cataract patients (9/145). In addition, genetic and allelic heterogeneities existed among the childhood cataract patients. The nonsense and frameshift variants had greater effects on the AlphaFold2-modeled protein structures than the missense variants.

CONCLUSIONS

This study revealed that 35.17% (51/145) sporadic childhood cataract patients in southern China harbored damaging variants in cataract-related genes, expanding the genetic variation spectrum of childhood cataracts.

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来源期刊

American Journal of Ophthalmology 医学-眼科学

CiteScore

9.20

自引率

7.10%

发文量

406

审稿时长

36 days

期刊介绍： The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented online at www.AJO.com and on ScienceDirect. The American Journal of Ophthalmology publishes Full-Length Articles, Perspectives, Editorials, Correspondences, Books Reports and Announcements. Brief Reports and Case Reports are no longer published. We recommend submitting Brief Reports and Case Reports to our companion publication, the American Journal of Ophthalmology Case Reports. Manuscripts are accepted with the understanding that they have not been and will not be published elsewhere substantially in any format, and that there are no ethical problems with the content or data collection. Authors may be requested to produce the data upon which the manuscript is based and to answer expeditiously any questions about the manuscript or its authors.