{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:37:21Z","timestamp":1763552241995,"version":"3.40.5"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000913","82101153","81790643","82121003"],"award-info":[{"award-number":["82000913","82101153","81790643","82121003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder; however, the known FEVR\u2010associated variants account for approximately only 50% cases. Currently, the pathogenesis of most reported variants is not well studied, we aim to identify novel variants from FEVR\u2010associated genes and perform a comprehensive functional analysis to uncover the pathogenesis of variants that cause FEVR. Using targeted gene panel and Sanger sequencing, we identified six novel and three known variants in <jats:italic>TSPAN12<\/jats:italic> and <jats:italic>NDP<\/jats:italic>. These variants were demonstrated to cause significant inhibition of Norrin\/\u03b2\u2010catenin pathway by dual\u2010luciferase reporter assay and western blot analysis. Structural analysis and co\u2010immunoprecipitation revealed compromised interactions between missense variants and binding partners in the Norrin\/\u03b2\u2010catenin pathway. Immunofluorescence and subcellular protein extraction were performed to reveal the abnormal subcellular trafficking. Additionally, over\u2010expression of <jats:italic>TSPAN12<\/jats:italic> successfully enhanced the Norrin\/\u03b2\u2010catenin signaling activity by strengthening the binding affinity of mutant Norrin with FZD4 or LRP5. Together, these observations expanded the spectrum of FEVR\u2010associated variants for the genetic counseling and prenatal diagnosis of FEVR, as well providing a potential therapeutic strategy for the treatment of FEVR.<\/jats:p>","DOI":"10.1111\/cge.14273","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T12:42:29Z","timestamp":1669898549000},"page":"320-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A comprehensive functional analysis on the pathogenesis of novel <scp><i>TSPAN12<\/i><\/scp> and <scp><i>NDP<\/i><\/scp> variants in familial exudative vitreoretinopathy"],"prefix":"10.1111","volume":"103","author":[{"given":"Rulian","family":"Zhao","sequence":"first","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study and Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Provincial People's Hospital University of 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