{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:30:55Z","timestamp":1790641855622,"version":"4.1.0"},"reference-count":43,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002325","name":"Victorian Government, Operational Infrastructure Support","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002325","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian Government Research Training Program"},{"name":"NHMRC Senior Research Fellowship"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1116360"],"award-info":[{"award-number":["GNT1116360"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1185477"],"award-info":[{"award-number":["GNT1185477"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Ophth"],"accepted":{"date-parts":[[2022,8,5]]},"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Paediatric (childhood or congenital) cataract is an opacification of the normally clear lens of the eye and has a genetic basis in at least 18% of cases in Australia. This study aimed to replicate clinical gene screening to identify variants likely to be causative of disease in an Australian patient cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>Sixty-three reported isolated cataract genes were screened for rare coding variants in 37 Australian families using genome sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Disease-causing variants were confirmed in eight families with variant classification as \u2018likely pathogenic\u2019. This included novel variants <jats:italic>PITX3<\/jats:italic> p.(Ter303LeuextTer100), <jats:italic>BFSP1<\/jats:italic> p.(Glu375GlyfsTer2), and <jats:italic>GJA8<\/jats:italic> p.(Pro189Ser), as well as, previously described variants identified in genes <jats:italic>GJA3, GJA8, CRYAA, BFSP1, PITX3, COL4A1<\/jats:italic> and <jats:italic>HSF4<\/jats:italic>. Additionally, eight variants of uncertain significance with evidence towards pathogenicity were identified in genes: <jats:italic>GJA3, GJA8, LEMD2, PRX, CRYBB1, BFSP2,<\/jats:italic> and <jats:italic>MIP<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings expand the genotype\u2013phenotype correlations of both pathogenic and benign variation in cataract-associated genes. They further emphasise the need to develop additional evidence such as functional assays and variant classification criteria specific to paediatric cataract genes to improve interpretation of variants and molecular diagnosis in patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjophth-2022-001064","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T11:02:58Z","timestamp":1661511778000},"page":"e001064","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Pathogenic genetic variants identified in Australian families with paediatric cataract"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-9134","authenticated-orcid":false,"given":"Johanna L","family":"Jones","sequence":"first","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1940-0007","authenticated-orcid":false,"given":"Bennet J","family":"McComish","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-9359","authenticated-orcid":false,"given":"Sandra E","family":"Staffieri","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Ophthalmology, Royal Children's Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Souzeau","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S","family":"Kearns","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Royal Children's Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jac C","family":"Charlesworth","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Mackey","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B","family":"Ruddle","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Ophthalmology, Royal Children's Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Taranath","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pater","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Women\u2019s and Children\u2019s Hospital, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Casey","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Women\u2019s and Children\u2019s Hospital, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie E","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn P","family":"Burdon","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia"},{"name":"Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"2025090109541931000_7.1.e001064.1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.86.7.782"},{"key":"2025090109541931000_7.1.e001064.2","first-page":"2007","article-title":"Cat-map: putting cataract on the map","volume":"16","author":"Shiels","year":"2010","journal-title":"Mol Vis"},{"key":"2025090109541931000_7.1.e001064.3","first-page":"589","article-title":"Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population","volume":"22","author":"Li","year":"2016","journal-title":"Mol Vis"},{"key":"2025090109541931000_7.1.e001064.4","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/humu.24240","article-title":"Genome sequencing in congenital cataracts improves diagnostic yield","volume":"42","author":"Ma","year":"2021","journal-title":"Hum Mutat"},{"key":"2025090109541931000_7.1.e001064.5","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2025090109541931000_7.1.e001064.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"2025090109541931000_7.1.e001064.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"2025090109541931000_7.1.e001064.8","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"2025090109541931000_7.1.e001064.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2025090109541931000_7.1.e001064.10","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-134"},{"key":"2025090109541931000_7.1.e001064.11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"2025090109541931000_7.1.e001064.12","doi-asserted-by":"crossref","first-page":"W535","DOI":"10.1093\/nar\/gkab354","article-title":"PredictProtein - Predicting Protein Structure and Function for 29 Years","volume":"49","author":"Bernhofer","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2025090109541931000_7.1.e001064.13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-548"},{"key":"2025090109541931000_7.1.e001064.14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg595"},{"key":"2025090109541931000_7.1.e001064.15","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2025090109541931000_7.1.e001064.16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2025090109541931000_7.1.e001064.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.04.003"},{"key":"2025090109541931000_7.1.e001064.18","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/gim.2018.42","article-title":"The ACMG\/AMP reputable source criteria for the interpretation of sequence variants","volume":"20","author":"Biesecker","year":"2018","journal-title":"Genet Med"},{"key":"2025090109541931000_7.1.e001064.19","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1534\/g3.117.300109","article-title":"High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia","volume":"7","author":"Javadiyan","year":"2017","journal-title":"G3"},{"key":"2025090109541931000_7.1.e001064.20","doi-asserted-by":"publisher","DOI":"10.1086\/379381"},{"key":"2025090109541931000_7.1.e001064.21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0072518","article-title":"Mutations in the EphA2 gene are a major contributor to inherited cataracts in south-eastern Australia","volume":"8","author":"Dave","year":"2013","journal-title":"PLoS One"},{"key":"2025090109541931000_7.1.e001064.22","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.88.1.79"},{"key":"2025090109541931000_7.1.e001064.23","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/eye.2017.268","article-title":"A novel missense mutation in HSF4 causes autosomal-dominant congenital lamellar cataract in a British family","volume":"32","author":"Berry","year":"2018","journal-title":"Eye"},{"key":"2025090109541931000_7.1.e001064.24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0013"},{"key":"2025090109541931000_7.1.e001064.25","doi-asserted-by":"crossref","DOI":"10.3390\/genes12040580","article-title":"Molecular and genetic mechanism of non-syndromic congenital cataracts. mutation screening in Spanish families","volume":"12","author":"Fern\u00e1ndez-Alcalde","year":"2021","journal-title":"Genes"},{"key":"2025090109541931000_7.1.e001064.26","first-page":"1343","article-title":"A novel mutation in the connexin 46 (GJA3) gene associated with congenital cataract in a Chinese pedigree","volume":"17","author":"Ding","year":"2011","journal-title":"Mol Vis"},{"key":"2025090109541931000_7.1.e001064.27","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.713284","article-title":"Broadening the mutation spectrum in GJA8 and CHMP4b: novel missense variants and the associated phenotypes in six Chinese Han congenital cataracts families","volume":"8","author":"Wang","year":"2021","journal-title":"Front Med"},{"key":"2025090109541931000_7.1.e001064.28","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/13816810.2019.1675179","article-title":"Identification and preliminary functional analysis of two novel congenital cataract associated mutations of cx46 and Cx50","volume":"40","author":"Ye","year":"2019","journal-title":"Ophthalmic Genet"},{"key":"2025090109541931000_7.1.e001064.29","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/02713683.2019.1675176","article-title":"A novel mutation p.S93R in CRYBB1 associated with dominant congenital cataract and microphthalmia","volume":"45","author":"Jin","year":"2020","journal-title":"Curr Eye Res"},{"key":"2025090109541931000_7.1.e001064.30","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1289-0"},{"key":"2025090109541931000_7.1.e001064.31","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.bbrc.2018.10.066","article-title":"Molecular mechanism of aquaporin 0-induced fiber cell to fiber cell adhesion in the eye lens","volume":"506","author":"Varadaraj","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2025090109541931000_7.1.e001064.32","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/ajmg.c.31837","article-title":"Molecular diagnostic challenges for non-retinal developmental eye disorders in the United Kingdom","volume":"184","author":"Jackson","year":"2020","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025090109541931000_7.1.e001064.33","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21191"},{"key":"2025090109541931000_7.1.e001064.34","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2010.42"},{"key":"2025090109541931000_7.1.e001064.35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/mgg3.181","article-title":"Hutterite-type cataract maps to chromosome 6p21.32-p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death","volume":"4","author":"Boone","year":"2016","journal-title":"Mol Genet Genomic Med"},{"key":"2025090109541931000_7.1.e001064.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.06.036"},{"key":"2025090109541931000_7.1.e001064.37","first-page":"376","article-title":"A novel missense mutation in the gene for gap-junction protein alpha3 (GJA3) associated with autosomal dominant \"nuclear punctate\" cataracts linked to chromosome 13q","volume":"10","author":"Bennett","year":"2004","journal-title":"Mol Vis"},{"key":"2025090109541931000_7.1.e001064.38","first-page":"1837","article-title":"Molecular analysis of cataract families in India: new mutations in the CRYBB2 and GJA3 genes and rare polymorphisms","volume":"16","author":"Santhiya","year":"2010","journal-title":"Mol Vis"},{"key":"2025090109541931000_7.1.e001064.39","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"2025090109541931000_7.1.e001064.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"2025090109541931000_7.1.e001064.41","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"2025090109541931000_7.1.e001064.42","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176601"},{"key":"2025090109541931000_7.1.e001064.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"}],"container-title":["BMJ Open Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjophth-2022-001064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T16:54:33Z","timestamp":1756745673000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjophth.bmj.com\/lookup\/doi\/10.1136\/bmjophth-2022-001064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,8,26]]},"published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1136\/bmjophth-2022-001064"],"URL":"https:\/\/doi.org\/10.1136\/bmjophth-2022-001064","relation":{},"ISSN":["2397-3269"],"issn-type":[{"value":"2397-3269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}