{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:51:22Z","timestamp":1790509882558,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital cataract is causing one\u2010third of blindness worldwide. Congenital cataract is heterogeneous in its inheritance patterns. The current study is aimed to explore the unknown genetic causes underlying congenital cataracts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples from affected and normal individuals of n\u00a0=\u00a025 Pakistani families identified with congenital cataracts were collected. Genomic DNA was extracted and Sanger sequencing was performed to identify novel pathogenic variants in the <jats:italic>FYCO1<\/jats:italic> (MIM#607182) gene. Later structural bioinformatics tools and molecular dynamics simulations were performed to analyze the impact of these variants on protein structure and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sanger sequencing resulted in the identification of a novel splice site mutation (NM_024513.3: c.3151\u201029_3151\u20107del) segregating in an autosomal recessive manner. This novel variant was confirmed to be absent in the n\u00a0=\u00a0300 population controls. Further, bioinformatics tools revealed the formation of a mutant protein with a loss of the Znf domain. In addition, we also found a previously known (c.4127\u2009T\u2009&gt;\u2009C; p.Leu1376Pro) mutation in four families. We also report a novel heterozygous variant (c.3419G\u2009&gt;\u2009A; p.Arg1140Gln) in another family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, we report a novel deletion (NM_024513.3: c.3151\u201029_3151\u20107del) in one family and a frequent homozygous missense mutation (c.4127\u2009T\u2009&gt;\u2009C; p.Leu1376Pro) in four Pakistani families. The current research highlights the importance of autophagy in lens development and maintaining its transparency.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1985","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T09:50:05Z","timestamp":1653990605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeted gene sequencing of <i>FYCO1<\/i> identified a novel mutation in a Pakistani family for autosomal recessive congenital cataract"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-3478","authenticated-orcid":false,"given":"Rani Saira","family":"Saleem","sequence":"first","affiliation":[{"name":"School of Biochemistry and Biotechnology University of Punjab  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorath Noorani","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology and Strabismus Al\u2010Shifa Eye Trust Hospital  Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-8281","authenticated-orcid":false,"given":"Saba","family":"Irshad","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Biotechnology University of Punjab  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3614-0702","authenticated-orcid":false,"given":"Naeem Mahmood","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology University of Gujrat  Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arslan","family":"Hamid","sequence":"additional","affiliation":[{"name":"LIMES Institute University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Azmat Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology University of Gujrat  Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Imran","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazia","family":"Micheal","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics AcademicMedical Centre  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43042\u2010022\u201000272\u20102"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31822623d5"},{"key":"e_1_2_13_4_1","first-page":"2931","article-title":"Novel crystallin gamma B mutations in a Kuwaiti family with autosomal dominant congenital cataracts reveal genetic and clinical heterogeneity","volume":"18","author":"AlFadhli S.","year":"2012","journal-title":"Molecular Vision"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2021.1955277"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.051029"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00833-w"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.2.213"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.127"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.52"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa977"},{"key":"e_1_2_13_12_1","first-page":"1705","article-title":"Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia","volume":"16","author":"Br\u00e9mond\u2010Gignac D.","year":"2010","journal-title":"Molecular Vision"},{"key":"e_1_2_13_13_1","first-page":"1773","article-title":"Spatial expression patterns of autophagy genes in the eye lens and induction of autophagy in lens cells","volume":"18","author":"Brennan L. A.","year":"2012","journal-title":"Molecular Vision"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.008"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-21469"},{"key":"e_1_2_13_16_1","first-page":"1359","article-title":"A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family","volume":"15","author":"Chen Q.","year":"2009","journal-title":"Molecular Vision"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1019"},{"key":"e_1_2_13_18_1","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 X.","year":"2011","journal-title":"Molecular Vision"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2012.707273"},{"issue":"4","key":"e_1_2_13_20_1","first-page":"515","article-title":"A novel pathogenic mutation of CRYGD gene in a congenital cataract family","volume":"33","author":"Gao M.","year":"2016","journal-title":"Zhonghua yi xue yi Chuan xue za zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics"},{"issue":"10","key":"e_1_2_13_21_1","first-page":"1333","article-title":"A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation: Evidence of clinical heterogeneity","volume":"13","author":"Gonzalez\u2010Huerta L. M.","year":"2007","journal-title":"Molecular Vision"},{"key":"e_1_2_13_22_1","first-page":"1651","article-title":"A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family","volume":"13","author":"Gu F.","year":"2007","journal-title":"Molecular Vision"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.21"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-3149"},{"key":"e_1_2_13_25_1","first-page":"334","article-title":"Mutations in FYCO1 identified in families with congenital cataracts","volume":"26","author":"Iqbal H.","year":"2020","journal-title":"Molecular Vision"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20545"},{"key":"e_1_2_13_27_1","first-page":"511","article-title":"Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family","volume":"16","author":"Kaul H.","year":"2010","journal-title":"Molecular Vision"},{"issue":"5","key":"e_1_2_13_28_1","first-page":"650","article-title":"Use of high\u2010throughput targeted exome sequencing in genetic diagnosis of Chinese family with congenital cataract","volume":"9","author":"Ma M. F.","year":"2016","journal-title":"International Journal of Ophthalmology"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn845"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9020112"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.08.019"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200907015"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1481"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1086\/519980"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-38938-3_1"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_13_37_1","first-page":"762","volume-title":"Pediatric ophthalmology and strabismus","author":"Vander Veen D. K.","year":"2012"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.31033\/ijrasb.8.2.2"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-016-0001-8"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3213"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0910-814"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2013.811260"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30064"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1985","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1985","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1985","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T13:18:13Z","timestamp":1692796693000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/mgg3.1985"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1985","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,31]]},"assertion":[{"value":"2021-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1985"}}