Analysis of gene mutation spectrum for early-onset high myopia based on whole-exome sequencing

作者：Liyin Wang, Jian Cao, Dongmei Yang, Yanze Yu, Zhanying Wang, Shilai Xing, Mingcheng Wang, Xiaoguang Yu, Xingtao Zhou, Jing Zhao · 发表于：British Journal of Ophthalmology · 年份：2025 · DOI：10.1136/bjo-2025-327552 · 被引用次数：1 · 研究领域：Ophthalmology and Visual Impairment Studies、Corneal surgery and disorders、Connexins and lens biology

Aim This study aimed to identify the loci of gene mutations associated with high myopia, analyse the genetic mutation spectrum characteristics for early onset high myopia (eo-HM) and explore the application of polygenic risk scores (PRSs) in predicting eo-HM. Methods Whole-exome sequencing (WES) and ophthalmic measurements were performed on participants with high myopia, and the mutation results were further verified by copy number variation sequencing, long range PCR and Sanger sequencing. Participants were classified into eo-HM (onset age<7 years and binocular spherical equivalent refraction <−6.0 dioptres (D)) and late-onset high myopia (lo-HM). PRS was calculated and assessed for eo-HM prediction accuracy through receiver operating characteristic (ROC) curve metrics. Results The participants comprised 100 patients with high myopia. WES identified 36 variants across 35 of 100 patients (35.00%), with the eo-HM group exhibiting a significantly higher detection rate (56.52%) than the lo-HM group (16.67%) (p<0.001). COL2A1 c.1221+1G>A, ARR3 c.41T>C, GLRA2 c.1006G>A, ZEB1 c.1672C>T and HDAC8 c.466A>G were recognised as de novo mutation loci in eo-HM. TCF7L2, AIPL1, INPP5E and the promoter mutation of SALL4 were identified as novel potential pathogenic mutations for high myopia (HM). Genetic mutations related to retinal diseases were more frequently observed in the eo-HM group than in the lo-HM group (p<0.01). ROC curve analysis signified that PRS had ...