{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:38:34Z","timestamp":1777660714717,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Familial exudative vitreoretinopathy (FEVR, OMIM 133780) is a severe inherited eye disease characterized by abnormal development of the retinal vasculature. Variants in the reported genes account for \u223c50% of total FEVR cases. However, the pathogenesis of the other 50% of FEVR cases remains unclear. Therefore, it is crucial to identify novel variants responsible for the pathogenesis of FEVR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>To find causative variants responsible for FEVR in two Han Chinese families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>We recruited two families with FEVR patients and applied exome sequencing on the genomic DNA samples from the probands. Sanger sequencing was performed for variant validation. Western blot analysis and luciferase assays were performed to test the expression levels and activity of the mutant proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified two novel missense variants in the\n                      <jats:italic toggle=\"yes\">LRP5<\/jats:italic>\n                      gene (NM_002335), c.1176 C\u2009&gt;\u2009A (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p.Asp392Glu\">p.Asp392Glu<\/jats:ext-link>\n                      ) and c.2435\u2009A&gt;C (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p.Asp812Ala\">p.Asp812Ala<\/jats:ext-link>\n                      ), both inherited in an autosomal dominant manner. Both variants significantly reduced Norrin\/\u03b2-catenin signaling activity without affecting the expression of the LRP5 protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This study expands the variant spectrum of the\n                      <jats:italic toggle=\"yes\">LRP5<\/jats:italic>\n                      gene for FEVR, providing valuable information for prenatal counseling and molecular diagnosis of FEVR.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/gtmb.2021.0223","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T11:29:15Z","timestamp":1646393355000},"page":"146-151","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Two Novel Variants in the\n                    <i>LRP5<\/i>\n                    Gene that Cause Familial Exudative Vitreoretinopathy"],"prefix":"10.1177","volume":"26","author":[{"given":"Yuze","family":"Wang","sequence":"first","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rulian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erkuan","family":"Dai","sequence":"additional","affiliation":[{"name":"Ophthalmology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Peng","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."},{"name":"Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqi","family":"He","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."},{"name":"Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6001-6827","authenticated-orcid":false,"given":"Mu","family":"Yang","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."},{"name":"Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-3776","authenticated-orcid":false,"given":"Shujin","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China."},{"name":"Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.09.003"},{"key":"e_1_3_4_3_1","first-page":"473","article-title":"Familial exudative vitreoretinopathy","volume":"93","author":"Benson WE","year":"1995","unstructured":"Benson WE (1995) Familial exudative vitreoretinopathy. 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