Abstract
Background
High myopia is a major cause of visual impairment, and genetic factors play crucial roles in the pathogenesis. We performed this study to identify candidate genes for the development of high myopia in a four-generation Chinese family with myopia.
Methods
All family members with myopia and 100 healthy participants were included in this study. Data were obtained on demographics, disease history, and ocular examination results. We performed whole exome sequencing of the genomic DNA and Sanger sequencing to verify the variants. Functional analyses of the variant were performed using software programmes.
Results
Nine of thirteen family members were found to have high myopia, amongst which two members were also diagnosed keratoconus. A missense variant in the keratin 12 gene (KRT12, p.Val410Gly) was detected in all high myopia cases but not in other family members without high myopia or the controls. The variant was predicted to be benign by online software programmes. However, modelling of the three-dimensional structure of the protein clearly revealed conformational changes caused by the mutation.
Conclusions
A missense mutation in the KRT12 gene was identified in this Chinese family, which may be associated with the pathogenesis of high myopia.
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Data availability
The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors would like to express their gratitude to all of the study participants for their cooperation.
Funding
This study received partial funding support from the following projects. The National Natural Science Foundation of China (Grant No. 82305379); the China National Postdoctoral Programme for Innovative Talents (Grant No. BX20230095); China Postdoctoral Science Foundation (Grant No. 2023M740740); National Natural Science Foundation of China for Young Scholars (No. 82000929); the National Natural Science Foundation of China (No. 81770955); the Shanghai Sailing Programme (No. 20YF1405000); the Project of Shanghai Science and Technology (No. 20410710100); the Clinical Research Plan of SHDC (No. SHDC2020CR1043B); the Project of Shanghai Xuhui District Science and Technology (No. 2020-015); the Project of Shanghai Xuhui District Science and Technology (No. XHLHGG202104); the Shanghai Engineering Research Centre of Laser and Autostereoscopic 3D for Vision Care (No. 20DZ2255000); and the construction of a 3D digital intelligent prevention and control platform for the whole life cycle of highly myopic patients in the Yangtze River Delta (No. 21002411600).
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QL, TH, XW and XP: Data collection, analyses, and manuscript writing. QL: Project management and study; Methodology. XW: Software Operation. XZ: Manuscript review and editing. All of the authors read and approved the final manuscript.
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Lin, Q., Wang, X., Han, T. et al. A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia. Eye 38, 3290–3295 (2024). https://doi.org/10.1038/s41433-024-03279-8
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DOI: https://doi.org/10.1038/s41433-024-03279-8