Expanding the Phenotypic and Genotypic Landscape of Nonsyndromic High Myopia: A Cross-Sectional Study in 731 Chinese Patients

Abstract

PURPOSE. High myopia (HM) is defined as a refractive error worse than À6.00 diopter (D). This study aims to update the phenotypic and genotypic landscape of nonsyndromic HM and to establish a biological link between the phenotypic traits and genetic deficiencies. METHODS. A cross-sectional study involving 731 participants varying in refractive error, axial length (AL), age, myopic retinopathy, and visual impairment. The phenotypic traits were analyzed by four ophthalmologists while mutational screening was performed in eight autosomal causative genes. Finally, we assessed the clinical relevance of identified mutations under the guidance of the American College of Medical Genetics and Genomics. RESULTS. The relationship between refractive error and AL varied in four different age groups ranging from 3-to 85-years old. In adult groups older than 21 years, 1-mm increase in AL conferred 10.84% higher risk of pathologic retinopathy (Category ‡2) as well as 7.35% higher risk of low vision (best-corrected visual acuities <0.3) with P values < 0.001. The prevalence rates of pathologic retinopathy and low vision both showed a nonlinear positive correlation with age. Forty-five patients were confirmed to harbor pathogenic mutations, including 20 novel mutations. These mutations enriched the mutational pool of nonsyndromic HM to 1.5 times its previous size and enabled a statistically significant analysis of the genotypephenotype correlation. Finally, SLC39A5, CCDC111, BSG, and P4HA2 were more relevant to eye elongation, while ZNF644, SCO2, and LEPREL1 appeared more relevant to refracting media. CONCLUSIONS. Our findings shed light on how multiple HM-related phenotypes are associated with each other and their link with gene variants.

Nonhuman Primate Model of Oculocutaneous Albinism with TYR and OCA2 Mutations

“…The three-dimensional homology modeling of the candidate proteins was analyzed by using SwissProt and visualized with the PyMOL algorithm. Then, the pathogenicity of the identified causative mutations was predicted using multiple bioinformatics programs, including MutationTaster, Muta-tionAssessor, and SIFT, as described previously [68,69].…”

Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

“…Tran-Viet et al (2013) observed Sco2 protein localization in the retina, retinal pigment epithelium (RPE), and scleral wall in mouse ocular tissues. We further identified mutations A201P and I221V in SCO2 in 2019 (Cai et al, 2019c). Here, a new variant c.518A>T (p.D173V) in SCO2 is detected.…”

“…Up to now, only a few genes responsible for non-syndromic myopia have been discovered. In our previous study of large-scale screening of eight causative genes in 731 patients with HM, we merely identified mutations in 6.16% cases (Cai et al, 2019c). In this study, we identified four new candidate genes associated with HM.…”

Reducing the Global Burden of Myopia by Delaying the Onset of Myopia and Reducing Myopic Progression in Children

“…11 Among Chinese adults 21 years of age and older, a 1-mm increase in axial length conferred a 10.84% higher risk of pathologic myopic retinopathy as well as a 7.35% higher risk of low vision. 55 Pathologic myopia is an important cause of low vision and blindness, especially in East Asia, where it is responsible for 12.2% to 31.25% of cases of low vision 11,56e59 and was ranked as the most frequent cause of blindness in one Chinese study (19.4%). 60 The Rotterdam Study found that myopic degeneration was the most common cause of visual impairment (25%) among those younger than 75 years of age in The Netherlands.…”