{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:59Z","timestamp":1753869719845,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["2019\u201012M\u20105\u2010032"],"award-info":[{"award-number":["2019\u201012M\u20105\u2010032"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2021JDGD0036","2021YFS0369","2022YFS0598"],"award-info":[{"award-number":["2021JDGD0036","2021YFS0369","2022YFS0598"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81790643","82000913","82101153","82121003"],"award-info":[{"award-number":["81790643","82000913","82101153","82121003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial exudative vitreoretinopathy (FEVR) is an inherited blinding eye disease with abnormal retinal vascular development. We aim to broaden the variant spectrum of FEVR and provide a basis for molecular diagnosis and genetic consultation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited five FEVR patients from one large Chinese family. Whole\u2010exome sequencing (WES) and Sanger sequencing were applied to sequence, analyze, and verify variants on genomic DNA samples. Immunocytochemistry, western blot, qPCR, and luciferase assay were performed to test the influence of the variant on the protein expression and activity of the Norrin\/\u03b2\u2010catenin pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel heterozygous frameshift variant c.533dupC (p.D179Rfs*6) in Tetraspanin 12 (<jats:italic>TSPAN12<\/jats:italic>) gene that is related to FEVR. This variant caused degradation of the entire TSPAN12 protein, which failed to activate Norrin\/\u03b2\u2010catenin signaling, possibly causing FEVR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed a novel frameshift variant D179Rfs*6 in <jats:italic>TSPAN12<\/jats:italic> that is inherited in an autosomal dominant manner. We found that D179Rfs*6 caused a failure to activate Norrin\/\u03b2\u2010catenin signaling. This finding broadens the variant spectrum of <jats:italic>TSPAN12<\/jats:italic> and provides invaluable information for the molecular diagnosis of FEVR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1949","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:44:34Z","timestamp":1649857474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel frameshift variant in the <i>TSPAN12<\/i> gene causes autosomal dominant <scp>FEVR<\/scp>"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7041-9267","authenticated-orcid":false,"given":"Li","family":"Peng","sequence":"first","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu China"},{"name":"Natural Products Research Center, 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