{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:37:21Z","timestamp":1792802241374,"version":"4.5.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010009","name":"Heilongjiang Provincial Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["LBH-Q17106"],"award-info":[{"award-number":["LBH-Q17106"]}],"id":[{"id":"10.13039\/501100010009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research and Innovation Fund of the First Affiliated Hospital of Harbin Medical University","award":["2017Y008"],"award-info":[{"award-number":["2017Y008"]}],"id":[{"id":"https:\/\/ror.org\/05vy2sc54","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically review the relationship between genotypes and clinical phenotypes of Familial exudative vitreoretinopathy (FEVR) to support risk estimation and therapeutic decisions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review with meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>The data of our study were collected from PubMed, Embase, Web of Science, Cochrane, CBM, China National Knowledge Infrastructure (CNKI), WAN FANG and VIP databases since inception to August 2021.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 3257 patients from 32 studies were included according to the inclusion and exclusion criteria. Among all the cases, the mutation frequencies of LRP5, FZD4, NDP, TSPAN12, ZNF408 and KIF11 were 13.6%, 11.5%, 4.6%, 6.7%, 1.6%, and 5.7%, respectively. We found that the patients with NDP and FZD4 suffer more severe symptoms, among which 86.4% patients of NDP and 78.6% patients of FZD4 were in the advanced stage of FEVR. Retinal detachment is the most frequent symptom with patients of LRP5 and NDP mutations, accounting for 51.9% and 64.5%, respectively. For the patients with the mutation of TSPAN12, retinal fold is the most common clinical manifestation, and suffer the mildest clinical phenotypes compared with the other three genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results of the meta-analysis indicate that different types of genetic mutations occur at different frequencies. In addition, the clinical manifestations of FEVR are related to the type of gene mutation. Therefore, targeted treatment strategies and follow-up recommendations should be adopted for different pathogenic genes of FEVR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0271326","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T13:35:01Z","timestamp":1657719301000},"page":"e0271326","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Genotype-phenotype associations in familial exudative vitreoretinopathy: A systematic review and meta-analysis on more than 3200 individuals"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-1445","authenticated-orcid":true,"given":"Xiaona","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1956-9507","authenticated-orcid":true,"given":"Xuhui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"pone.0271326.ref001","doi-asserted-by":"crossref","first-page":"107720","DOI":"10.1016\/j.exer.2019.107720","article-title":"Symmetry of folds in FEVR: A genotype-phenotype correlation study","volume":"186","author":"Z Wang","year":"2019","journal-title":"Exp Eye Res"},{"key":"pone.0271326.ref002","doi-asserted-by":"crossref","first-page":"107941","DOI":"10.1016\/j.exer.2020.107941","article-title":"The spectrum of genetic mutations in patients with asymptomatic mild familial exudative vitreoretinopathy","volume":"192","author":"C Chen","year":"2020","journal-title":"Exp Eye Res"},{"issue":"13","key":"pone.0271326.ref003","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1167\/iovs.17-23541","article-title":"Spectrum of Variants in 389 Chinese Probands With Familial Exudative Vitreoretinopathy","volume":"59","author":"J-K Li","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0271326.ref004","first-page":"917","article-title":"Novel mutations in FZD4 and phenotype-genotype correlation in Chinese patients with familial exudative vitreoretinopathy","volume":"22","author":"M Tang","year":"2016","journal-title":"Mol Vis"},{"key":"pone.0271326.ref005","first-page":"517","article-title":"Diversity of familial exudative vitreoretinopathy","author":"C Chen","year":"2019","journal-title":"Chinese Journal of Ocular Fundus Diseases"},{"issue":"7","key":"pone.0271326.ref006","doi-asserted-by":"crossref","first-page":"980","DOI":"10.3390\/genes12070980","article-title":"Whole-Gene Deletions of FZD4 Cause Familial Exudative Vitreoretinopathy","volume":"12","author":"L Huang","year":"2021","journal-title":"Genes (Basel)"},{"key":"pone.0271326.ref007","unstructured":"Chunli Chen. 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