{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:11:09Z","timestamp":1784718669571,"version":"3.55.0"},"reference-count":30,"publisher":"BMJ","issue":"9","funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"crossref","award":["2020A1515011282"],"award-info":[{"award-number":["2020A1515011282"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Program of Guangzhou","award":["202102010209"],"award-info":[{"award-number":["202102010209"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,2,8]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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. <jats:italic>Psmd3<\/jats:italic> knock-in mice with point mutation were generated for measuring myopia-related parameters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We screened a novel <jats:italic>PSMD3<\/jats:italic> variant (c.689T&gt;C; p.F230S) in a Chinese family with PM, and another rare mutation (c.1015C&gt;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 <jats:italic>PSMD3<\/jats:italic> 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&lt;0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A new potential pathogenic gene, <jats:italic>PSMD3<\/jats:italic>, in a PM family was identified, and it may be involved in the elongation of AL and the development of PM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108978","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T13:20:35Z","timestamp":1679491235000},"page":"918-924","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["<i>PSMD3<\/i> gene mutations cause pathological myopia"],"prefix":"10.1136","volume":"60","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lian","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiling","family":"Yu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan 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