{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:12:20Z","timestamp":1773724340265,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Congenital cataracts are a significant cause of visual impairment or blindness in children. One-third of cases estimated to have a genetic cause. We carried out gene analysis and bioinformatics analysis to map the locus and to identify the underlying genetic defect in a 12-member, four-generation Chinese family affected with bilateral congenital cataracts. We screened individuals of the family and discovered a distinct missense mutation in HSF4 (a gene at this locus that encodes teat-shock transcription factor 4). Bioinformatics analysis was used to determine possible changes in the protein structure that could affect the phenotype. Sequencing of the candidate genes showed a heterozygous c.69 G\u2192T change in the heat shock transcription factor 4 (HSF4) gene, which resulted in the substitution of a lysine with an asparagine (p. K23N). This mutation cosegregated with all affected individuals and was not observed in unaffected family members. Bioinformatics analysis indicated that the p. K23N mutation was predicted to be disease causing. This is the first report of the novel missense mutation, c.69 G\u2192T (p. K23N), in exon 3 of the HSF4 locus on 16q21-q22 associated with bilateral congenital cataracts in a Chinese family. This novel mutation could enable propergenetic diagnostics and counseling in affected families and could lead to a better understanding of the structure and function of HSF4 in health and disease.<\/jats:p>","DOI":"10.1534\/g3.113.009860","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T21:35:24Z","timestamp":1395178524000},"page":"823-828","source":"Crossref","is-referenced-by-count":13,"title":["A Novel <i>HSF4<\/i> Gene Mutation Causes Autosomal-Dominant Cataracts in a Chinese Family"],"prefix":"10.1093","volume":"4","author":[{"given":"Huibin","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhike","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haining","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, WeiHaiWei People's Hospital, 264200, Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchen","family":"You","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinping","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"},{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2021042011315036000_bib1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations.","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"2021042011315036000_bib2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bioinformatics\/bti770","article-title":"The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.","volume":"22","author":"Arnold","year":"2006","journal-title":"Bioinformatics"},{"key":"2021042011315036000_bib3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/jcb.10023","article-title":"Heat shock proteins of adult and embryonic human ocular lenses.","volume":"84","author":"Bagchi","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"2021042011315036000_bib4","first-page":"1705","article-title":"Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia.","volume":"16","author":"Bremond-Gignac","year":"2010","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/ng921","article-title":"Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract.","volume":"31","author":"Bu","year":"2002","journal-title":"Nat. Genet."},{"key":"2021042011315036000_bib6","first-page":"1157","article-title":"Crystallin gene mutations in Indian families with inherited pediatric cataract.","volume":"14","author":"Devi","year":"2008","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib7","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s00439-005-1309-9","article-title":"Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations.","volume":"117","author":"Forshew","year":"2005","journal-title":"Hum. Genet."},{"key":"2021042011315036000_bib8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/jmg.37.7.481","article-title":"The genetics of childhood cataract.","volume":"37","author":"Francis","year":"2000","journal-title":"J. Med. Genet."},{"key":"2021042011315036000_bib9","first-page":"159","article-title":"Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2.","volume":"41","author":"Gill","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2021042011315036000_bib10","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis"},{"key":"2021042011315036000_bib11","first-page":"1033","article-title":"The congenital \u201cant-egg\u201d cataract phenotype is caused by a missense mutation in connexin46.","volume":"12","author":"Hansen","year":"2006","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib12","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":"2021042011315036000_bib13","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1086\/302619","article-title":"The gamma-crystallins and human cataracts: a puzzle made clearer.","volume":"65","author":"Heon","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"2021042011315036000_bib14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1076\/opep.10.2.67.13894","article-title":"Birth prevalence of visually significant infantile cataract in a defined U.S. population.","volume":"10","author":"Holmes","year":"2003","journal-title":"Ophthalmic Epidemiol."},{"key":"2021042011315036000_bib15","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ajo.2006.03.056","article-title":"Novel HSF4 mutation causes congenital total white cataract in a Chinese family.","volume":"142","author":"Ke","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"2021042011315036000_bib16","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/hmg\/6.5.665","article-title":"Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2.","volume":"6","author":"Litt","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"2021042011315036000_bib17","first-page":"1154","article-title":"Two Chinese families with pulverulent congenital cataracts and deltaG91 CRYBA1 mutations.","volume":"13","author":"Lu","year":"2007","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib18","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1463-5224.2006.00496.x","article-title":"Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts.","volume":"9","author":"Mellersh","year":"2006","journal-title":"Vet. Ophthalmol."},{"key":"2021042011315036000_bib19","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1128\/MCB.17.1.469","article-title":"HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator.","volume":"17","author":"Nakai","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2021042011315036000_bib20","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s00417-011-1781-y","article-title":"A new locus in chromosome 2q37-qter is associated with posterior polar cataract.","volume":"250","author":"Ouyang","year":"2012","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"2021042011315036000_bib21","first-page":"2108","article-title":"Congenital and infantile cataract in the United Kingdom: underlying or associated factors. British Congenital Cataract Interest Group.","volume":"41","author":"Rahi","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2021042011315036000_bib22","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.survophthal.2004.02.013","article-title":"Molecular genetic basis of inherited cataract and associated phenotypes.","volume":"49","author":"Reddy","year":"2004","journal-title":"Surv. Ophthalmol."},{"key":"2021042011315036000_bib23","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/hmg\/ddh110","article-title":"Characterization of the G91del CRYBA1\/3-crystallin protein: a cause of human inherited cataract.","volume":"13","author":"Reddy","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2021042011315036000_bib24","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":"2021042011315036000_bib25","first-page":"851","article-title":"A novel GJA8 mutation causing a recessive triangular cataract.","volume":"14","author":"Schmidt","year":"2008","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib26","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations.","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat. Methods"},{"key":"2021042011315036000_bib27","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server.","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2021042011315036000_bib28","first-page":"1850","article-title":"Mutation screening of HSF4 in 150 age-related cataract patients.","volume":"14","author":"Shi","year":"2008","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib29","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1001\/archopht.125.2.165","article-title":"Genetic origins of cataract.","volume":"125","author":"Shiels","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"2021042011315036000_bib30","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1086\/519980","article-title":"CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q.","volume":"81","author":"Shiels","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021042011315036000_bib31","author":"Smaoui","year":"2004"},{"key":"2021042011315036000_bib32","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ygeno.2006.02.012","article-title":"Early transposable element insertion in intron 9 of the Hsf4 gene results in autosomal recessive cataracts in lop11 and ldis1 mice.","volume":"88","author":"Talamas","year":"2006","journal-title":"Genomics"},{"key":"2021042011315036000_bib33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1034\/j.1399-0004.1999.560507.x","article-title":"Genetic and segregation analysis of congenital cataract in the Indian population.","volume":"56","author":"Vanita","year":"1999","journal-title":"Clin. Genet."},{"key":"2021042011315036000_bib34","first-page":"518","article-title":"A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family.","volume":"12","author":"Vanita","year":"2006","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib35","first-page":"70","article-title":"A novel mutation in MIP associated with congenital nuclear cataract in a Chinese family.","volume":"17","author":"Wang","year":"2011","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib36","first-page":"2096","article-title":"A novel deletion variant of gammaD-crystallin responsible for congenital nuclear cataract.","volume":"13","author":"Zhang","year":"2007","journal-title":"Mol. Vis."},{"key":"2021042011315036000_bib37","first-page":"265","article-title":"An autosomal dominant cataract locus mapped to 19q13-qter in a Chinese family.","volume":"17","author":"Zhao","year":"2011","journal-title":"Mol. Vis."}],"container-title":["G3 Genes|Genomes|Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/4\/5\/823\/37179534\/g3journal0823.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/4\/5\/823\/37179534\/g3journal0823.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T14:16:39Z","timestamp":1618928199000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/4\/5\/823\/6025831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1534\/g3.113.009860","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,5,1]]},"published":{"date-parts":[[2014,5,1]]}}}