{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:17:11Z","timestamp":1792181831618,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Wagner vitreoretinopathy (WVR) is a rare autosomal dominant vitreoretinopathy caused by pathogenic variants in the <jats:italic>VCAN<\/jats:italic> gene. The aim of this study was to report a novel splicing variant in <jats:italic>VCAN<\/jats:italic> identified in a three\u2010generation Chinese family initially diagnosed with familial exudative vitreoretinopathy and to describe the patients' clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four affected individuals from a three\u2010generation family underwent detailed ophthalmic examinations, including best\u2010corrected visual acuity by Snellen E chart, slit\u2010lamp biomicroscopy, indirect ophthalmoscopy under pupil dilatation, ocular B\u2010ultrasonography, optical coherence tomography scans, and fundus autofluorescence. Targeted next\u2010generation sequencing was performed to identify variants of the disease\u2010causing gene for the proband, followed by co\u2010segregation analysis using Sanger\u2010DNA sequencing. Reverse transcriptase\u2010polymerase chain reaction (RT\u2010PCR) was carried out to verify the effects of a variant on <jats:italic>VCAN<\/jats:italic> pre\u2010mRNA splicing in the lymphocytes from the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected a novel heterozygous variant c.4004\u20104_c.4004\u20103delinsCA of <jats:italic>VCAN<\/jats:italic> in all four affected individuals. RT\u2010PCR revealed that the novel variant caused an abnormal splicing in exon 8 of the <jats:italic>VCAN<\/jats:italic> and imbalanced versican transcripts. All four patients presented vitreous syneresis and bilateral retinal detachment occurring at different ages. The patients also showed different extents of visual defects and diverse clinical manifestations, including cataract, iris\u2013lens synechiae, inverted papillae, and ectopic foveas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results expand the mutation spectrum of <jats:italic>VCAN<\/jats:italic> and further confirm that the splicing sites for exon 8 are mutation hot spots. Patients with WVR may present high phenotype variation; therefore, molecular analysis is very important for precise diagnosis of patients with inherited vitreoretinopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2083","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T07:35:55Z","timestamp":1667633755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel splicing variant of <i>VCAN<\/i> identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-7684","authenticated-orcid":false,"given":"Junwei","family":"Zhong","sequence":"first","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shi","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical College of Ophthalmology Tianjin Medical University  Tianjin China"},{"name":"Nankai University Eye Hospital  Tianjin China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology &amp; Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"GeneReviews\u00ae","author":"Adam M. 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