{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T12:00:07Z","timestamp":1781265607247,"version":"3.54.1"},"reference-count":55,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010907","name":"University Postgraduate Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010907","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/Y034325\/1"],"award-info":[{"award-number":["MR\/Y034325\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Retinitis Pigmentosa Fighting Blindness and Fight for Sight UK","award":["RP Genome Project GR586"],"award-info":[{"award-number":["RP Genome Project GR586"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,11,17]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Familial exudative vitreoretinopathy (FEVR) is an inherited eye disease characterised by the incomplete development of the retinal vasculature. Over 10 genes have been associated with FEVR, but there are still a substantial number of genetically unsolved cases. The aim of this study was to analyse whole genome sequencing (WGS) data from the FEVR cases in the Genomics England (GEL) 100\u2009000 genomes project to identify the causative variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WGS was performed by GEL and accessed within the GEL Research Environment. FEVR cases were identified using LabKey and candidate variants were extracted using the \u2018gene-variant workflow\u2019 and \u2018CNV\/SV workflow\u2019 and by using BCFtools in unfiltered VCF files.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-nine FEVR probands were submitted to GEL. We found six novel and eight previously reported pathogenic variants in six genes known to underlie FEVR (\n                      <jats:italic>TSPAN12, LRP5, FZD4, CTNNB1, KIF11<\/jats:italic>\n                      and\n                      <jats:italic>NDP<\/jats:italic>\n                      ), as well as structural variants in\n                      <jats:italic>TSPAN12<\/jats:italic>\n                      and\n                      <jats:italic>KIF11<\/jats:italic>\n                      . These accounted for 15\/59 (25.4%) of FEVR cases. We also found candidate heterozygous variants in\n                      <jats:italic>CTNND1<\/jats:italic>\n                      in three unsolved FEVR cases. Expanding the list of genes examined to include all genes reported to be mutated in ocular disorders likely solved a further four cases, indicating that these individuals may be misclassified as FEVR in GEL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      By performing bespoke reanalysis of the FEVR GEL cohort, this study has highlighted additional heterozygous variants in\n                      <jats:italic>CTNND1<\/jats:italic>\n                      in FEVR cases and increased the diagnostic yield from 20% solved by the GEL analysis pipeline to 37% (22\/59), but the majority of FEVR cases remain without a molecular diagnosis.\n                    <\/jats:p>\n                  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Identifying and characterising the genes and proteins underlying coats disease and familial exudative vitreoretinopathy (FEVR). PhD, University of Leeds; 2018. Available: https:\/\/etheses.whiterose.ac.uk\/id\/eprint\/23070\/1\/Thesis%20Denisa%20Dzulova%202018%20Post-VIVA%20PRINT%20FINAL.pdf"},{"key":"2026061204451529000_63.3.187.53","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1498-1"},{"key":"2026061204451529000_63.3.187.54","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1038\/ejhg.2016.99","article-title":"An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients","volume":"24","author":"Bonnet","year":"2016","journal-title":"Eur J Hum Genet"},{"key":"2026061204451529000_63.3.187.55","doi-asserted-by":"publisher","DOI":"10.1086\/302855"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2025-111083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:45:49Z","timestamp":1781264749000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2025-111083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2,20]]},"published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1136\/jmg-2025-111083"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2025-111083","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}