{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:55:28Z","timestamp":1768316128791,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61373048"],"award-info":[{"award-number":["61373048"]}],"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;amp; Gen Med"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the <jats:italic>TSPAN12<\/jats:italic> causes difference in clinical manifestations between individuals in the same family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Next\u2010generation sequencing (NGS)\u2010based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel heterozygous missense mutation (c.1A&gt;G, p.M1V) localized in the start codon of the <jats:italic>TSPAN12<\/jats:italic> and was detected as a potentially disease\u2010causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high\u2010stage FEVR fundus changes coupled with a sharp decline in vision.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a novel start codon mutation (c.1A&gt;G, p.M1V) in the <jats:italic>TSPAN12<\/jats:italic> that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of <jats:italic>TSPAN12<\/jats:italic>, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin\u201012 protein in the pathogenesis of FEVR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.948","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T03:14:32Z","timestamp":1566875672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A start codon mutation of the <i>TSPAN12<\/i> gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy"],"prefix":"10.1002","volume":"7","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"BGI Education Center University of Chinese Academy of Sciences Shenzhen China"},{"name":"He's university Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwei","family":"Wang","sequence":"additional","affiliation":[{"name":"BGI Education Center University of Chinese Academy of Sciences Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"He's university Shenyang China"},{"name":"Shenyang He Eye Specialist Hospital Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoshi","family":"Wang","sequence":"additional","affiliation":[{"name":"He's university Shenyang China"},{"name":"Shenyang He Eye Specialist Hospital Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyue","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lusheng","family":"Wang","sequence":"additional","affiliation":[{"name":"He's university Shenyang China"},{"name":"Department of Computer Science City University of Hong Kong Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Li","sequence":"additional","affiliation":[{"name":"He's university Shenyang China"},{"name":"Department of Computer Science City University of Hong Kong Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"He's university Shenyang China"},{"name":"Shenyang He Eye Specialist Hospital Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1205"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/1.7.461"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1976.03910040034006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(69)91237-9"},{"key":"e_1_2_9_8_1","volume-title":"RetNet: Retinal information network. Na+ Ca2, 5","author":"Daiger S. P.","year":"2013"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.123471"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.04.038"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2014.70"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)70899-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx070"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.04.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.029"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.08.010"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<45:AID-HUMU10>3.0.CO;2-T"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1113"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-016-0236-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.64.2.112"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(98)96002-X"},{"key":"e_1_2_9_24_1","first-page":"487","article-title":"Persistent hyperplastic primary vitreous: Diagnosis, treatment and results","volume":"95","author":"Pollard Z. F.","year":"1997","journal-title":"Transactions of the American Ophthalmological Society"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds197"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21324"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng957"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3638"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20585"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15680"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22577"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/383202"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)76893-X"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813217115"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00216-8"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.948","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T10:56:42Z","timestamp":1708513002000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,26]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/mgg3.948"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.948","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,26]]},"assertion":[{"value":"2019-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00948"}}