{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:57:17Z","timestamp":1776268637934,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2018YSZH0020"],"award-info":[{"award-number":["2018YSZH0020"]}],"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":["81700876"],"award-info":[{"award-number":["81700876"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial exudative vitreoretinopathy (FEVR, OMIM 133780) is a severe hereditary retinal disease characterized by incomplete retinal vascular development and pathological neovascularization. It has been reported that variants in nine genes are associated with FEVR, but they can only explain approximately 50% of FEVR patients, suggesting that other FEVR\u2010associated variants or genes remain to be discovered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) was carried out to analyse genomic DNA samples from the probands of 68 families with FEVR. Sanger sequencing was used to verify all identified variants. Western blot analysis was utilized to detect the expression of the variant mutant proteins. A luciferase assay was conducted to test the receptor activity of the mutant <jats:italic>FZD4<\/jats:italic> proteins in Norrin\u2010\u03b2\u2010catenin signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven heterozygous <jats:italic>FZD4<\/jats:italic> variants were found to cause FEVR in seven families, including six missense variants and one deletion variant: c.182C&gt;T (p.T61I), c.205C&gt;T (p.H69Y), c.217_234del (p.73T_78Qdel), c.264C&gt;A (p.Y88X), c.344G&gt;T (p.G115V), c.678G&gt;A (p.W226X) and c.1310T&gt;C (p.I437T). Among these variants, c.205C&gt;T (p.H69Y) and c.678G&gt;A (p.W226X) are known FEVR\u2010causing variants, while the other five variants are novel pathogenic variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed the cause of FEVR in seven Chinese families and identified five novel pathogenic variants in <jats:italic>FZD4<\/jats:italic>, which expanded the mutation spectrum of FEVR in the Chinese population. These findings also provided further support for using WES in the clinical diagnosis of FEVR.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.13690","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T15:38:50Z","timestamp":1574696330000},"page":"356-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of novel variants in the <i>FZD4<\/i> gene associated with familial exudative vitreoretinopathy in Chinese families"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1858-1822","authenticated-orcid":false,"given":"Huijuan","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Chengdu Biology Chinese Academy of Sciences  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Human Disease Gene Study, 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