Next-Generation Sequencing Screening of 43 Families with Non-Syndromic Early-Onset High Myopia: A Clinical and Genetic Study

Abstract

Early-onset high myopia (EoHM) is a disease that causes a spherical refraction error of ≥−6 diopters before 10 years of age, with potential multiple ocular complications. In this article, we report a clinical and genetic study of 43 families with EoHM recruited in our center. A complete ophthalmological evaluation was performed, and a sample of peripheral blood was obtained from proband and family members. DNA was analyzed using a customized next-generation sequencing panel that included 419 genes related to ophthalmological disorders with a suspected genetic cause, and genes related to EoHM pathogenesis. We detected pathogenic and likely pathogenic variants in 23.9% of the families and detected variants of unknown significance in 76.1%. Of these, 5.7% were found in genes related to non-syndromic EoHM, 48.6% in genes associated with inherited retinal dystrophies that can include a syndromic phenotype, and 45.7% in genes that are not directly related to EoHM or retinal dystrophy. We found no candidate genes in 23% of the patients, which suggests that further studies are needed. We propose a systematic genetic analysis for patients with EoHM because it helps with follow-up, prognosis and genetic counseling.

Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia

“…In the case of EoHM, however, given the young age of the patients, environmental factors are not considered to have a significant influence on the development of myopia. This suggests that there is a greater genetic burden involved in EoHM, supporting a genetic approach to the disease [3].…”

“…From a physiological point of view, it involves a refractive error where the light rays entering the eye focus on a point in front of the retina, leading to decreased visual acuity. This refractive error is due to a postnatal axial elongation of the eye in the process of emmetropization [2,3]. Although myopia is usually considered a benign condition that can be corrected with the use of glasses, contact lenses or refractive surgery, it is becoming a public health concern due to its increasing prevalence in younger populations and its progression to its most severe and pathological form, high myopia (HM) (Figure 1).…”

“…This study focuses on early-onset HM (EoHM), which occurs in children under 10 years of age [3]. Through an examination of the disease from a genetic perspective, this analysis seeks to contribute to a better understanding of the role of genetics in its development.…”

“…Based on current trends, the study by Holden et al, estimates that the number of people affected will significantly increase worldwide by 2050, as may be observed in Figure 2 [4,6]. This study focuses on early-onset HM (EoHM), which occurs in children under 10 years of age [3]. Through an examination of the disease from a genetic perspective, this analysis seeks to contribute to a better understanding of the role of genetics in its development.…”

“…Currently, the most studied environmental factor believed to protect individuals from developing myopia is the time spent outdoors [4]. Conversely, several studies have linked the progression of myopia to the time spent in near work and exposure to artificial light [3,5]. In the case of EoHM, however, given the young age of the patients, environmental factors are not considered to have a significant influence on the development of myopia.…”