{
  "abstract": "Aim This study aimed to identify the loci of gene mutations associated with high myopia, analyse the genetic mutation spectrum characteristics for early onset high myopia (eo-HM) and explore the application of polygenic risk scores (PRSs) in predicting eo-HM.Methods Whole-exome sequencing (WES) and ophthalmic measurements were performed on participants with high myopia, and the mutation results were further verified by copy number variation sequencing, long range PCR and Sanger sequencing. Participants were classified into eo-HM (onset age<7 years and binocular spherical equivalent refraction <−6.0 dioptres (D)) and late-onset high myopia (lo-HM). PRS was calculated and assessed for eo-HM prediction accuracy through receiver operating characteristic (ROC) curve metrics.Results The participants comprised 100 patients with high myopia. WES identified 36 variants across 35 of 100 patients (35.00%), with the eo-HM group exhibiting a significantly higher detection rate (56.52%) than the lo-HM group (16.67%) (p<0.001). COL2A1 c.1221+1G>A, ARR3 c.41T>C, GLRA2 c.1006G>A, ZEB1 c.1672C>T and HDAC8 c.466A>G were recognised as de novo mutation loci in eo-HM. TCF7L2, AIPL1, INPP5E and the promoter mutation of SALL4 were identified as novel potential pathogenic mutations for high myopia (HM). Genetic mutations related to retinal diseases were more frequently observed in the eo-HM group than in the lo-HM group (p<0.01). ROC curve analysis signified that PRS had acceptable predicting ability for eo-HM (area under the curve=0.70).Conclusion This study expands the eo-HM mutational spectrum and proposes novel HM pathogenic genes. PRS demonstrates a certain ability to predict eo-HM.",
  "authors": [
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Liyin Wang"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Jian Cao"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China",
        "Second People’s Hospital of Yunnan Province, Affiliated Hospital of Yunnan University, Yunnan, China"
      ],
      "name": "Dongmei Yang"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Yanze Yu"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Zhanying Wang"
    },
    {
      "affiliations": [
        "Institute of PSI Genomics Co., Ltd, Wenzhou, China"
      ],
      "name": "Shilai Xing"
    },
    {
      "affiliations": [
        "Institute of PSI Genomics Co., Ltd, Wenzhou, China"
      ],
      "name": "Mingcheng Wang"
    },
    {
      "affiliations": [
        "Institute of PSI Genomics Co., Ltd, Wenzhou, China"
      ],
      "name": "Xiaoguang Yu"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Xingtao Zhou"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China",
        "Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China"
      ],
      "name": "Jing Zhao"
    }
  ],
  "title": "Analysis of gene mutation spectrum for early-onset high myopia based on whole-exome sequencing",
  "uid": "92f26790-69ed-5370-9858-12d75346da29"
}