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Original research
PSMD3 gene mutations cause pathological myopia
  1. Jing Chen,
  2. Ping Lian,
  3. Xiujuan Zhao,
  4. Jun Li,
  5. Xiling Yu,
  6. Xia Huang,
  7. Shida Chen,
  8. Lin Lu
  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, Guangdong, China
  1. Correspondence to Dr Lin Lu, Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou 510060, Guangdong, China; lulin{at}; Dr Shida Chen; chenshd3{at}


Purpose Genetic factors play a prominent role in the pathogenesis of pathological myopia (PM). However, the exact genetic mechanism of PM remains unclear. This study aimed to determine the candidate mutation of PM in a Chinese family and explore the potential mechanism.

Methods We performed exome sequencing and Sanger sequencing in a Chinese family and 179 sporadic PM cases. The gene expression in human tissue was investigated by RT-quantitative real-time PCR (RT-qPCR) and immunofluorescence. Cell apoptotic rates were tested by annexin V-APC/7AAD and flow cytometry. Psmd3 knock-in mice with point mutation were generated for measuring myopia-related parameters.

Results We screened a novel PSMD3 variant (c.689T>C; p.F230S) in a Chinese family with PM, and another rare mutation (c.1015C>A; p.L339M) was identified in 179 unrelated cases with PM. RT-qPCR and immunofluorescence confirmed the expression of PSMD3 in human eye tissue. Mutation of PSMD3 decreased the mRNA and protein expression, causing apoptosis of human retinal pigment epithelial cells. In in vivo experiments, the axial length (AL) of mutant mice increased significantly compared with that of wild-type mice (p<0.001).

Conclusions A new potential pathogenic gene, PSMD3, in a PM family was identified, and it may be involved in the elongation of AL and the development of PM.

  • Eye Diseases
  • Genetics
  • Point Mutation

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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  • JC and PL contributed equally.

  • Contributors Conceptualisation, supervision and writing (review and editing): JC, PL, SC and LL; data curation: JC, PL, JL and XH; data analysis: JC, PL, XZ and JL; investigation: JC, PL, JL and XY; methodology: JC, PL, XZ and XY; resources: JC, PL, JL and SC; visualisation: JC, PL and XZ; writing (original draft): JC and PL; LL acted as guarantor.

  • Funding This study was supported by the Natural Science Foundation of Guangdong province of China (2020A1515011282), the Science and Technology Program of Guangzhou (202102010209) and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology. The sponsor or funding organisation had no role in the design or conduct of this research.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.