{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:34:06Z","timestamp":1790274846744,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds of State Key Laboratory of Ophthalmology, research funds of Sun Yat-sen University","award":["15ykjxc22d"],"award-info":[{"award-number":["15ykjxc22d"]}]},{"name":"The grant from the National Natural Science Foundation of China","award":["31800873"],"award-info":[{"award-number":["31800873"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25\/696). Among 25 KIF11 mutations, 80% (20\/25) carried variants of loss of function and 48% (12\/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31\/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1\/70) of eyes with FEVR with mutations in other genes (p &lt; 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12\/70) of eyes with KIF11-associated retinopathy, and in 50% (39\/78) of eyes with FEVR with mutations in other genes (p &lt; 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.<\/jats:p>","DOI":"10.3390\/genes13040713","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T22:04:02Z","timestamp":1650319442000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Update on the Phenotypic and Genotypic Spectrum of KIF11-Related Retinopathy"],"prefix":"10.3390","volume":"13","author":[{"given":"You","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songshan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4936-3315","authenticated-orcid":false,"given":"Xiaoyan","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Xianlie S Road, Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/nature03503","article-title":"The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks","volume":"435","author":"Kapitein","year":"2005","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ajhg.2011.12.018","article-title":"Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy","volume":"90","author":"Ostergaard","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1002\/ajmg.a.36707","article-title":"Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: Five novel mutations and review of the literature","volume":"164A","author":"Mirzaa","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1001\/jamaophthalmol.2014.2814","article-title":"Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations","volume":"132","author":"Robitaille","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.preteyeres.2018.11.008","article-title":"Wnt Signaling in vascular eye diseases","volume":"70","author":"Wang","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1016\/j.ophtha.2011.06.020","article-title":"Clinical presentation of familial exudative vitreoretinopathy","volume":"118","author":"Ranchod","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1093\/hmg\/ddy244","article-title":"An FEVR-associated mutation in ZNF408 alters the expression of genes involved in the development of vasculature","volume":"27","author":"Karjosukarso","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","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":"Li","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1167\/iovs.17-22577","article-title":"Mutation Spectrum of the LRP5, NDP, and TSPAN12 Genes in Chinese Patients With Familial Exudative Vitreoretinopathy","volume":"58","author":"Tang","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.1167\/iovs.17-21679","article-title":"Novel Insights Into the Phenotypical Spectrum of KIF11-Associated Retinopathy, Including a New Form of Retinal Ciliopathy","volume":"58","author":"Birtel","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, Z., Chen, C., Sun, L., Zhang, A., Liu, C., Huang, L., and Ding, X. (2019). Symmetry of folds in FEVR: A genotype-phenotype correlation study. Exp. Eye Res., 186.","DOI":"10.1016\/j.exer.2019.107720"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1001\/archopht.1965.00970030171006","article-title":"Paving-Stone Degeneration of the Retina","volume":"73","author":"Allen","year":"1965","journal-title":"Arch. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1167\/iovs.14-15821","article-title":"Posterior pole retinal abnormalities in mild asymptomatic FEVR","volume":"56","author":"Yuan","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/eye.2014.70","article-title":"Familial exudative vitreoretinopathy and related retinopathies","volume":"29","author":"Gilmour","year":"2015","journal-title":"Eye"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1167\/tvst.8.2.21","article-title":"An Ophthalmic Targeted Exome Sequencing Panel as a Powerful Tool to Identify Causative Mutations in Patients Suspected of Hereditary Eye Diseases","volume":"8","author":"Wang","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1167\/iovs.14-14880","article-title":"Evaluation of 12 myopia-associated genes in Chinese patients with high myopia","volume":"56","author":"Li","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_17","unstructured":"(2022, March 17). Human Gene Mutation Database. Available online: http:\/\/www.hgmd.cf.ac.uk\/ac\/index.php."},{"key":"ref_18","unstructured":"(2022, March 17). Genome Aggregation Database. Available online: https:\/\/gnomad.broadinstitute.org."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, C., Sun, L., Li, S., Huang, L., Zhang, T., Wang, Z., Yu, B., Luo, X., and Ding, X. (2020). Novel variants in familial exudative vitreoretinopathy patients with KIF11 mutations and the Genotype-Phenotype correlation. Exp. Eye Res., 199.","DOI":"10.1016\/j.exer.2020.108165"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, J.K., Fei, P., Li, Y., Huang, Q.J., Zhang, Q., Zhang, X., Rao, Y.Q., Li, J., and Zhao, P. (2016). Identification of novel KIF11 mutations in patients with familial exudative vitreoretinopathy and a phenotypic analysis. Sci. Rep., 6.","DOI":"10.1038\/srep26564"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Menon, M., Mohammadi, S., Davila-Velderrain, J., Goods, B.A., Cadwell, T.D., Xing, Y., Stemmer-Rachamimov, A., Shalek, A.K., Love, J.C., and Kellis, M. (2019). Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-12780-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/ejhg.2013.263","article-title":"Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): Review of phenotype associated with KIF11 mutations","volume":"22","author":"Jones","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1136\/bjophthalmol-2015-306878","article-title":"KIF11 mutations are a common cause of autosomal dominant familial exudative vitreoretinopathy","volume":"100","author":"Hu","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ophtha.2017.02.005","article-title":"Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease","volume":"124","author":"Taylor","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"845","DOI":"10.4103\/1673-5374.158351","article-title":"Inhibition of kinesin-5 improves regeneration of injured axons by a novel microtubule-based mechanism","volume":"10","author":"Baas","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajo.2011.06.002","article-title":"Clinical features of congenital retinal folds","volume":"153","author":"Nishina","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00439-010-0848-x","article-title":"CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation","volume":"128","author":"Mukhopadhyay","year":"2010","journal-title":"Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/ncb3201","article-title":"An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes","volume":"17","author":"Wheway","year":"2015","journal-title":"Nat. Cell Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/4\/713\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:56:07Z","timestamp":1760136967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/4\/713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,18]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["genes13040713"],"URL":"https:\/\/doi.org\/10.3390\/genes13040713","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,18]]}}}