Whole-exome sequencing for the genetic diagnosis of early-onset high myopia and associated hereditary eye disorders

Identification of genetic variations associated with early-onset high myopia (eoHM) provides a genetic basis for risk assessment and prevention of this disease. Whole-exome sequencing (WES) was performed on 41 probands with eoHM with or without other abnormalities. Sixteen high myopia-associated variants identified in 13 probands involved 13 genes comprising 11 autosomal dominant and 2 X-linked genes. The frequency of variants in SNRNP200, ARR3, and COL2A1 was 13%, which was slightly greater than that of other genes. A total of 46% were associated with inherited retinal diseases documented in the RetNet database. According to the relevant guidelines and standards, 9.7%(4/41) of the probands had suspected genetic pathogenic variations through combined clinical-genetic assessment (ID2,3,8,11). Interestingly, we found that the genetic diagnosis rate was significantly correlated with the specific clinical phenotypic characteristics of the patients. The diagnosis rate of patients with ultrahigh myopia was significantly greater than that of patients with high myopia. Genetic analysis identified the pathogenic factors of many cases of eoHM, revealing a strong association between eoHM candidate genes and hereditary retinal diseases. EoHM is the predominant clinical presentation in most hereditary ocular diseases.