{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:59:54Z","timestamp":1781067594151,"version":"3.54.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Congenital cataract is an important cause of childhood visual impairment, and genetic factors contribute substantially to its etiology. We report a boy aged 4\u20135 years with congenital cataract from a family with an apparent autosomal dominant inheritance pattern. Comprehensive ophthalmic examinations were performed in the proband and available relatives. Whole-exome sequencing (WES) in the proband identified several candidate variants, including a heterozygous\n                    <jats:italic>CRYGD<\/jats:italic>\n                    c.391T&amp;gt;C (p.Trp131Arg) variant. Subsequent Sanger sequencing was used to validate the candidate variants and assess segregation in available family members. The\n                    <jats:italic>CRYGD<\/jats:italic>\n                    c.391T&amp;gt;C (p.Trp131Arg) variant was present in all tested affected family members and absent in the tested unaffected relative, supporting co-segregation with the disease phenotype in this pedigree. Additional variants identified by WES, including\n                    <jats:italic>ITM2B<\/jats:italic>\n                    c.537C&amp;gt;G (p.Asn179Lys) and\n                    <jats:italic>ASB10<\/jats:italic>\n                    c.1402T&amp;gt;C (p.Ter468GlnextTer6), showed segregation patterns that were less consistent with the familial phenotype. According to ACMG criteria, the\n                    <jats:italic>CRYGD<\/jats:italic>\n                    variant remained classified as a variant of uncertain significance. To provide limited biological context, we also reviewed a public gene expression dataset and found lens-enriched expression of\n                    <jats:italic>CRYGD<\/jats:italic>\n                    , consistent with its established role in lens biology. This case may provide useful evidence for future variant interpretation and genetic counseling in congenital cataract families carrying\n                    <jats:italic>CRYGD<\/jats:italic>\n                    variants; however, further functional studies are required to clarify the pathogenic significance of c.391T&amp;gt;C (p.Trp131Arg).\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1778174","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:29:28Z","timestamp":1781065768000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Identification of a CRYGD variant in a family with congenital cataract"],"prefix":"10.3389","volume":"13","author":[{"given":"Junjie","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan","place":["Shandong, China"]},{"name":"Department of Ophthalmology, Shandong First Medical University and Shandong Academy of Medical Science, Jinan","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Weifang Eye Hospital, National Key Clinical specialty, Zhengda Guangming Eye Group, Weifang","place":["Shandong, China"]},{"name":"Weifang Eye Institute, Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Weifang Eye Hospital, National Key Clinical specialty, Zhengda Guangming Eye Group, Weifang","place":["Shandong, China"]},{"name":"Weifang Eye Institute, Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan","place":["Shandong, China"]},{"name":"Department of Ophthalmology, Shandong First Medical University and Shandong Academy of Medical Science, Jinan","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Weifang Eye Hospital, National Key Clinical specialty, Zhengda Guangming Eye Group, Weifang","place":["Shandong, China"]},{"name":"Weifang Eye Institute, Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Weifang Eye Hospital, National Key Clinical specialty, Zhengda Guangming Eye Group, Weifang","place":["Shandong, China"]},{"name":"Weifang Eye Institute, Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan","place":["Shandong, China"]},{"name":"Department of Ophthalmology, Shandong First Medical University and Shandong Academy of Medical Science, Jinan","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/eye.2016.156","article-title":"Global prevalence of childhood cataract: a systematic review","volume":"30","author":"Sheeladevi","year":"2016","journal-title":"Eye (London, England)."},{"key":"B2","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.semcdb.2007.10.003","article-title":"Congenital cataracts and their molecular genetics","volume":"19","author":"Hejtmancik","year":"2008","journal-title":"Semin Cell Dev Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1167\/iovs.64.2.5","article-title":"De Novo Mutations contributes approximately 7% of pathogenicity in inherited eye diseases","volume":"64","author":"Li","year":"2023","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1590\/S0004-27492011000200016","article-title":"The genetic and molecular basis of congenital cataract","volume":"74","author":"Santana","year":"2011","journal-title":"Arq Bras Oftalmol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/S0161-6420(94)31246-2","article-title":"Autosomal dominant congenital cataract","volume":"101","author":"Scott","year":"1994","journal-title":"Interocular Phenotyp. Variabil. Ophthalmol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/jmg.40.4.262","article-title":"Gamma-D crystallin gene (Crygd) mutation causes autosomal dominant congenital cerulean cataracts","volume":"40","author":"Nandrot","year":"2003","journal-title":"J Med Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.pbiomolbio.2014.02.006","article-title":"Functions of crystallins in and out of lens: roles in elongated and post-mitotic cells","volume":"115","author":"Slingsby","year":"2014","journal-title":"Prog Biophys Mol Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1086\/302619","article-title":"The gamma-crystallins and human cataracts: a puzzle made clearer","volume":"65","year":"1999","journal-title":"Am J Hum Genet."},{"key":"B9","first-page":"887","article-title":"A novel human crygd mutation in a juvenile autosomal dominant cataract","volume":"16","author":"Roshan","year":"2010","journal-title":"Mol Vis."},{"key":"B10","first-page":"2096","article-title":"Novel deletion variant of gammad-crystallin responsible for congenital nuclear cataract","volume":"13","author":"Zhang","year":"2007","journal-title":"Mol Vis."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.134292","article-title":"Truncation mutations of Crygd gene in congenital cataracts cause protein aggregation by disrupting the structural stability of \u0393d-crystallin","author":"Lin","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12886-025-03920-4","article-title":"Identification of mutations associated with congenital cataracts in nineteen Chinese families","volume":"25","author":"Sun","year":"2025","journal-title":"BMC Ophthalmol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12920-025-02255-9","article-title":"Genetic spectrum of congenital cataract with optional ocular and multisystem abnormalities","volume":"18","author":"Zhang","year":"2025","journal-title":"BMC Med Genomics."},{"key":"B14","doi-asserted-by":"publisher","first-page":"14380","DOI":"10.1038\/s41598-024-65227-6","article-title":"Deciphering the etiology of undiagnosed ocular anomalies along with systemic alterations in pediatric patients through whole exome sequencing","volume":"14","author":"Reyna-Fabi\u00e1n","year":"2024","journal-title":"Sci Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1111\/head.12246","article-title":"The care guidelines: consensus-based clinical case reporting guideline development","volume":"53","author":"Gagnier","year":"2013","journal-title":"Headache."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1086\/324158","article-title":"Alpha-B Crystallin gene (Cryab) mutation causes dominant congenital posterior polar cataract in humans","volume":"69","author":"Berry","year":"2001","journal-title":"Am J Hum Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/cge.12182","article-title":"Genetics of human cataract","volume":"84","author":"Shiels","year":"2013","journal-title":"Clin Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"107872","DOI":"10.1016\/j.exer.2019.107872","article-title":"Molecular genetics of congenital cataracts","volume":"191","author":"Li","year":"2020","journal-title":"Exp Eye Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1332992","DOI":"10.3389\/fmed.2024.1332992","article-title":"et al. Case report: whole exome sequencing identified a novel mutation (PY301h) of Maf in a Chinese family with congenital cataracts","volume":"11","author":"Lin","year":"2024","journal-title":"Front. Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2633004020938061","DOI":"10.1177\/2633004020938061","article-title":"Congenital cataract: a guide to genetic and clinical management","volume":"1","author":"Bell","year":"2020","journal-title":"Therapeutic Adv. Rare Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4759","DOI":"10.1007\/s10072-021-05480-z","article-title":"A novel homozygous variant in Jam3 gene causing hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (Hdbscc) with neonatal onset","volume":"42","author":"De Rose","year":"2021","journal-title":"Neurol. Sci. Off. J. Italian Neurol. Soc. Italian Soc. Clin. Neurophysiol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1778174\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:29:32Z","timestamp":1781065772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1778174\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":22,"alternative-id":["10.3389\/fmed.2026.1778174"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1778174","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"article-number":"1778174"}}