Mutation Screening of ARR3, CACNA1F, P4HA2, TRPM1, COL2A1, COL11A1 and PAX6 in a Chinese Cohort of 37 Patients with Early-Onset High Myopia.

Background/

Objectives

Early-onset high myopia (eoHM), defined as high myopia manifesting before 10 years of age, is largely attributed to genetic defects. This study aimed to investigate the genetic underpinnings of eoHM in a cohort of Chinese patients.

Methods

We recruited 64 Chinese patients with eoHM. Comprehensive clinical evaluations were performed, and whole exome sequencing (WES) was conducted to identify potential pathogenic variants. The genetic findings were analyzed and correlated with the clinical phenotypes.

Results

A total of 64 unrelated Chinese patients with suspected early-onset high myopia were initially recruited. Following whole exome sequencing (WES) and variant annotation, final 37 patients with variants in known myopia-associated genes were included in the analytical cohort. The mean age of onset for the cohort was 5 years (IQR, 4-7), with a mean spherical equivalent refraction of -7 D (IQR, (-8)-(-6)). Genetic analysis revealed variants in 28 known myopia-associated genes. We identified pathogenic or likely pathogenic variants in 11 of the 37 patients (29.7%, 95%CI: 0.1737-0.4590), while the overall diagnostic yield was 17.2% (11/64, 95%CI: 0.0970-0.2839) in initial 64 recruited patients. These genes included seven well-established eoHM-related genes, such as ARR3, CACNA1F, P4HA2, TRPM1, COL11A1, COL2A1, and PAX6. Additionally, variants of uncertain significance (VUS) in seven other candidate genes were detected in patients with eoHM.

Conclusions

Our findings expand the genetic spectrum of eoHM and reinforce the critical role of genetic testing in its etiological diagnosis and clinical management. Observed patterns of genotype-phenotype associations are descriptive and should be considered hypothesis-generating, requiring validation in larger cohorts. Additionally, we identify several candidate genes that may serve as prospective biomarkers, though these findings require validation in larger cohorts and functional studies.