{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:51Z","timestamp":1787028231839,"version":"build-2736575974"},"reference-count":20,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian National Program of Support to the Health Assistance of the Person with Deficiency (PRONAS\/PCD)","award":["25000.193451\/2019-21"],"award-info":[{"award-number":["25000.193451\/2019-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (CRYBB3) has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G&gt;A\/p.Gly156Glu in CRYBB3 in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of CRYBB3 is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G&gt;A\/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.<\/jats:p>","DOI":"10.3390\/genes12071069","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T02:28:01Z","timestamp":1626229681000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel Mutation in CRYBB3 Causing Pediatric Cataract and Microphthalmia"],"prefix":"10.3390","volume":"12","author":[{"given":"Olivia A.","family":"Zin","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza M.","family":"Neves","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-995X","authenticated-orcid":false,"given":"Fabiana L.","family":"Motta","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Ocular, S\u00e3o Paulo 04552-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafne D. G.","family":"Horovitz","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Guida","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1721-0608","authenticated-orcid":false,"given":"Leonardo H. F.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela P.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A.","family":"Zin","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"},{"name":"Instituto Catarata Infantil, Rio de Janeiro 22250-040, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-4447","authenticated-orcid":false,"given":"Juliana M. F.","family":"Sallum","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"},{"name":"Instituto de Gen\u00e9tica Ocular, S\u00e3o Paulo 04552-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-2224","authenticated-orcid":false,"given":"Zilton F. M.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Instituto Fernandes Figueira-Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","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"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jaapos.2012.09.004","article-title":"An update on progress and the changing epidemiology of causes of childhood blindness worldwide","volume":"16","author":"Kong","year":"2012","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-vision-091517-034346","article-title":"Biology of Inherited Cataracts and Opportunities for Treatment","volume":"5","author":"Shiels","year":"2019","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.ophtha.2004.06.024","article-title":"A nationwide Danish study of 1027 cases of congenital\/infantile cataracts: Etiological and clinical classifications","volume":"111","author":"Haargaard","year":"2004","journal-title":"Ophthalmology"},{"key":"ref_6","unstructured":"(2021, March 31). Cat-Map Complete List. Available online: https:\/\/cat-map.wustl.edu\/."},{"key":"ref_7","unstructured":"(2021, March 31). ABraOM: Brazilian Genomic Variants. Available online: http:\/\/abraom.ib.usp.br\/."},{"key":"ref_8","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":"ref_9","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1159\/000510481","article-title":"Molecular Etiology of Isolated Congenital Cataract Using Next-Generation Sequencing: Single Center Exome Sequencing Data from Turkey","volume":"11","author":"Sekeroglu","year":"2020","journal-title":"Mol. Syndr."},{"key":"ref_10","doi-asserted-by":"crossref","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."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1159\/000455752","article-title":"Inherited Congenital Cataract: A Guide to Suspect the Genetic Etiology in the Cataract Genesis","volume":"8","year":"2017","journal-title":"Mol. Syndr."},{"key":"ref_12","first-page":"5","article-title":"Molecular genetics of cataract","volume":"48","author":"Kannabiran","year":"2000","journal-title":"Indian J. Ophthalmol."},{"key":"ref_13","first-page":"415","article-title":"Short-range order of crystallin proteins accounts for eye lens transparency","volume":"302","author":"Delaye","year":"1983","journal-title":"Nat. Cell Biol."},{"key":"ref_14","first-page":"427","article-title":"Mutation screening of crystallin genes in Chinese families with congenital cataracts","volume":"25","author":"Zhuang","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","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":"ref_17","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1167\/iovs.04-1481","article-title":"Mutations in \u03b2B3-Crystallin Associated with Autosomal Recessive Cataract in Two Pakistani Families","volume":"46","author":"Riazuddin","year":"2005","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_18","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. Part C Semin. Med. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1038\/s41433-020-1115-6","article-title":"Cataract management in children: A review of the literature and current practice across five large UK centres","volume":"34","author":"Self","year":"2020","journal-title":"Eye"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.ophtha.2007.09.002","article-title":"Incidence of and Factors Associated with Glaucoma after Surgery for Congenital Cataract: Findings from the British Congenital Cataract Study","volume":"115","author":"Chak","year":"2008","journal-title":"Ophthalmology"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1069\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:07Z","timestamp":1760164207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":20,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["genes12071069"],"URL":"https:\/\/doi.org\/10.3390\/genes12071069","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,13]]}}}