Whole-Exome Sequencing Among School-Aged Children With High Myopia

Overview

Journal JAMA Netw Open

Publisher American Medical Association

Specialty General Medicine

Date 2023 Dec 1

PMID 38039006

Authors

Xiangyi Yu

Jian Yuan

Zhen Ji Chen

Kai Li

Yinghao Yao

Shilai Xing

Zhengbo Xue

Yue Zhang

Hui Peng

Gang An

Xiaoguang Yu

Jia Qu

Jianzhong Su

Affiliations

Soon will be listed here.

Abstract

Importance: High myopia (HM) is one of the leading causes of visual impairment worldwide. Genetic factors are known to play an important role in the development of HM.

Objective: To identify risk variants in a large HM cohort and to examine the implications of genetic testing of schoolchildren with HM.

Design, Setting, And Participants: This cohort study retrospectively reviewed whole-exome sequencing (WES) results in 6215 schoolchildren with HM who underwent genetic testing between September 2019 and July 2020 in Wenzhou City, China. HM is defined as a spherical equivalent refraction (SER) of -6.00 diopters (D) or less. The study setting was a genetic testing laboratory and a multicenter school census. Data were analyzed from July 2021 to June 2022.

Main Outcomes And Measures: The frequency and distribution of positive germline variants, the percentage of individuals with HM in both eyes, and subsequent variant yield for common high myopia (CHM; -8.00 D ≤ SER ≤ -6.00 D), ultra myopia (UM; -10.00 D ≤ SER < -8.00 D), and extreme myopia (EM; SER < -10.00 D).

Results: Of the 6215 schoolchildren with HM, 3278 (52.74%) were male. Their mean (SD) age was 14.87 (2.02) years, including 355 students in primary school, 1970 in junior high school, and 3890 in senior high school. The mean (SD) SER was -7.51 (-1.36) D for the right eye and -7.46 (-1.34) D for the left eye. Among schoolchildren with HM, genetic testing yielded 271 potential pathogenic variants in 75 HM candidate genes in 964 diagnoses (15.52%). A total of 36 known variants were found in 490 HM participants (7.88%) and 235 protein-truncating variants (PTVs) in 506 participants (8.14%). Involved variant yield was significantly positively associated with SER (Cochran-Armitage test for trend Z = 2.5492; P = .01), which ranged from 7.66% in the CHM group, 8.70% in the UM group, to 11.90% in the EM group. We also found that primary school students with EM had the highest variant yield of PTVs (8 of 35 students [22.86%]), which was 1.77 and 4.78 times that of the UM and CHM, respectively.

Conclusions And Relevance: In this cohort study of WES for HM, several potential pathogenic variants were identified in a substantial number of schoolchildren with HM. The high variation frequency in younger students with EM can provide clues for genetic screening and clinical examinations of HM to promote long-term follow-up assessment.

Citing Articles

Myopia in Children: Epidemiology, Genetics, and Emerging Therapies for Treatment and Prevention.

Surico P, Parmar U, Singh R, Farsi Y, Musa M, Maniaci A Children (Basel). 2025; 11(12.

PMID: 39767875 PMC: 11674392. DOI: 10.3390/children11121446.

Exome-wide genetic risk score (ExGRS) to predict high myopia across multi-ancestry populations.

Yuan J, Qiu R, Wang Y, Chen Z, Sun H, Dai W Commun Med (Lond). 2024; 4(1):280.

PMID: 39738800 PMC: 11685959. DOI: 10.1038/s43856-024-00718-1.

Diurnal gene expression patterns in retina and choroid distinguish myopia progression from myopia onset.

Stone R, Tobias J, Wei W, Carlstedt X, Zhang L, Iuvone P PLoS One. 2024; 19(7):e0307091.

PMID: 39028695 PMC: 11259283. DOI: 10.1371/journal.pone.0307091.

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