{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:17:15Z","timestamp":1779275835330,"version":"3.51.4"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100016806","name":"Natural Science Foundation of Nantong City","doi-asserted-by":"publisher","award":["222300420536"],"award-info":[{"award-number":["222300420536"]}],"id":[{"id":"10.13039\/100016806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["222102310307"],"award-info":[{"award-number":["222102310307"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["222102310599"],"award-info":[{"award-number":["222102310599"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.exer.2022.109342","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T19:41:09Z","timestamp":1670528469000},"page":"109342","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Trio-based exome sequencing broaden the genetic spectrum in keratoconus"],"prefix":"10.1016","volume":"226","author":[{"given":"Liyan","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenjiu","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengwei","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2022.109342_bib1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/ICO.0000000000002489","article-title":"Association of collagen gene (COL4A3) rs55703767 variant with response to riboflavin\/ultraviolet A-induced collagen cross-linking in female patients with keratoconus","volume":"40","author":"Abdelghany","year":"2021","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2022.109342_bib2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biochi.2013.09.015","article-title":"START ships lipids across interorganelle space","volume":"96","author":"Alpy","year":"2014","journal-title":"Biochimie"},{"key":"10.1016\/j.exer.2022.109342_bib3","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002645","article-title":"Role of titin missense variants in dilated cardiomyopathy","volume":"4","author":"Begay","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"10.1016\/j.exer.2022.109342_bib4","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbz155","article-title":"Current challenges and best-practice protocols for microbiome analysis","volume":"22","author":"Bharti","year":"2021","journal-title":"Briefings Bioinf."},{"key":"10.1016\/j.exer.2022.109342_bib5","doi-asserted-by":"crossref","DOI":"10.1038\/s41431-022-01087-w","article-title":"Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability","author":"Brea-Fernandez","year":"2022","journal-title":"Europ. J. Human Genetic. : EJHG (Eur. J. Hum. Genet.)"},{"key":"10.1016\/j.exer.2022.109342_bib6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.5005\/jp-journals-10025-1123","article-title":"Abnormal regulation of extracellular matrix and adhesion molecules in corneas of patients with keratoconus","volume":"5","author":"Bykhovskaya","year":"2016","journal-title":"Int. J. Keratoconus Ectatic Corneal Dis."},{"key":"10.1016\/j.exer.2022.109342_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108398","article-title":"Update on the genetics of keratoconus","volume":"202","author":"Bykhovskaya","year":"2021","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109342_bib8","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s40135-020-00253-x","article-title":"Omics analyses in keratoconus: from transcriptomics to proteomics","volume":"8","author":"Cai","year":"2020","journal-title":"Curr. Ophthalmol. Rep."},{"key":"10.1016\/j.exer.2022.109342_bib9","article-title":"Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile","volume":"11","author":"D'Souza","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109342_bib10","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/carcin\/bgaa017","article-title":"NDRG1 deficiency is associated with regional metastasis in oral cancer by inducing epithelial-mesenchymal transition","volume":"41","author":"de Lima","year":"2020","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.exer.2022.109342_bib11","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12881-020-01112-z","article-title":"Whole exome sequencing highlights variants in association with Keratoconus in Jordanian families","volume":"21","author":"Froukh","year":"2020","journal-title":"BMC Med. Genet."},{"key":"10.1016\/j.exer.2022.109342_bib12","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/ICO.0000000000000408","article-title":"Global consensus on keratoconus and ectatic diseases","volume":"34","author":"Gomes","year":"2015","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2022.109342_bib13","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/795738","article-title":"The genetic and environmental factors for keratoconus","volume":"2015","author":"Gordon-Shaag","year":"2015","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.exer.2022.109342_bib14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/s13023-020-01512-7","article-title":"Multi-level consistent changes of the ECM pathway identified in a typical keratoconus twin's family by multi-omics analysis","volume":"15","author":"Hao","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.exer.2022.109342_bib15","article-title":"Systematically displaying the pathogenesis of keratoconus via multi-level related gene enrichment-based review","volume":"8","author":"Hao","year":"2021","journal-title":"Front. Med."},{"key":"10.1016\/j.exer.2022.109342_bib16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s42003-021-01784-0","article-title":"A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus","volume":"4","author":"Hardcastle","year":"2021","journal-title":"Commun Biol"},{"key":"10.1016\/j.exer.2022.109342_bib17","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/aos.12302","article-title":"Visual performance and ocular abnormalities in deaf children and young adults: a literature review","volume":"92","author":"Hollingsworth","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"10.1016\/j.exer.2022.109342_bib18","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s42003-020-01137-3","article-title":"Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson","volume":"3","author":"Hosoda","year":"2020","journal-title":"Commun Biol"},{"key":"10.1016\/j.exer.2022.109342_bib19","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.ajhg.2011.09.014","article-title":"Mutation altering the miR-184 seed region causes familial keratoconus with cataract","volume":"89","author":"Hughes","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.exer.2022.109342_bib20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1083\/jcb.201408089","article-title":"ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores","volume":"212","author":"Isokane","year":"2016","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.exer.2022.109342_bib21","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ejhg.2017.4","article-title":"Collagen synthesis disruption and downregulation of core elements of TGF-beta, Hippo, and Wnt pathways in keratoconus corneas","volume":"25","author":"Kabza","year":"2017","journal-title":"Europ. J. Human Genetic. : EJHG (Eur. J. Hum. Genet.)"},{"key":"10.1016\/j.exer.2022.109342_bib22","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/jbmr.3233","article-title":"PLS3 deletions lead to severe spinal osteoporosis and disturbed bone matrix mineralization","volume":"32","author":"Kampe","year":"2017","journal-title":"J. Bone Miner. Res. : Off. J. Am. Soc. Bone Mineral Res."},{"key":"10.1016\/j.exer.2022.109342_bib23","doi-asserted-by":"crossref","first-page":"7687","DOI":"10.1167\/iovs.15-17538","article-title":"Variant c.2262A>C in DOCK9 leads to exon skipping in keratoconus family","volume":"56","author":"Karolak","year":"2015","journal-title":"Investigat. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.exer.2022.109342_bib24","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1167\/iovs.18-24267","article-title":"Differential expression of coding and long noncoding RNAs in keratoconus-affected corneas","volume":"59","author":"Khaled","year":"2018","journal-title":"Investigat. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.exer.2022.109342_bib25","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/7803029","article-title":"Molecular and histopathological changes associated with keratoconus","volume":"2017","author":"Khaled","year":"2017","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.exer.2022.109342_bib26","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1100\/tsw.2010.189","article-title":"Multifunctional receptor stabilin-1 in homeostasis and disease","volume":"10","author":"Kzhyshkowska","year":"2010","journal-title":"TheScientificWorldJOURNAL"},{"key":"10.1016\/j.exer.2022.109342_bib27","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.exer.2022.109342_bib28","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.exer.2022.109342_bib29","article-title":"Titin (TTN): from molecule to modifications, mechanics and medical significance","author":"Loescher","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.exer.2022.109342_bib30","first-page":"1","article-title":"Absence of significant genetic alterations in the VSX1, SOD1, TIMP3, and LOX genes in Brazilian patients with Keratoconus","author":"Lopes","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"10.1016\/j.exer.2022.109342_bib31","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1111\/jth.13799","article-title":"ARHGEF10 knockout inhibits platelet aggregation and protects mice from thrombus formation","volume":"15","author":"Lu","year":"2017","journal-title":"J. Thromb. Haemostasis"},{"key":"10.1016\/j.exer.2022.109342_bib32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-vision-121219-081723","article-title":"Genetic and environmental risk factors for keratoconus","volume":"6","author":"Lucas","year":"2020","journal-title":"Annu. Rev. Vis. Sci,"},{"key":"10.1016\/j.exer.2022.109342_bib33","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000017821","article-title":"The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: a prospective study","volume":"98","author":"Lyu","year":"2019","journal-title":"Medicine"},{"key":"10.1016\/j.exer.2022.109342_bib52","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.survophthal.2017.06.009","article-title":"A review of keratoconus: Diagnosis, pathophysiology, and genetics","volume":"62","author":"Mas Tur","year":"2017","journal-title":"Surv Ophthalmol"},{"key":"10.1016\/j.exer.2022.109342_bib34","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1001\/jamaophthalmol.2019.5293","article-title":"Association of genetic variation with keratoconus","volume":"138","author":"McComish","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.exer.2022.109342_bib35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fphys.2012.00037","article-title":"The sarcomeric protein nebulin: another multifunctional giant in charge of muscle strength optimization","volume":"3","author":"Ottenheijm","year":"2012","journal-title":"Front. Physiol."},{"key":"10.1016\/j.exer.2022.109342_bib36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0039-6257(97)00119-7","article-title":"Keratoconus","volume":"42","author":"Rabinowitz","year":"1998","journal-title":"Surv. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109342_bib37","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. : Off. J. Am. College Med. Genetics"},{"key":"10.1016\/j.exer.2022.109342_bib38","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.70870","article-title":"The cell adhesion molecule Sdk1 shapes assembly of a retinal circuit that detects localized edges","volume":"10","author":"Rochon","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.exer.2022.109342_bib39","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.rvsc.2022.04.006","article-title":"Upregulated genes in articular cartilage may help to counteract femoral head separation in broilers with 21 days of age","volume":"147","author":"Santos","year":"2022","journal-title":"Res. Vet. Sci."},{"key":"10.1016\/j.exer.2022.109342_bib40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/ICO.0000000000001083","article-title":"Trends in corneal transplantation in keratoconus","volume":"36","author":"Sarezky","year":"2017","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2022.109342_bib41","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1093\/hmg\/ddab075","article-title":"Pathogenic alleles in microtubule, secretory granule and extracellular matrix-related genes in familial keratoconus","volume":"30","author":"Shinde","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109342_bib42","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109342_bib43","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.4081\/cp.2018.1071","article-title":"SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment","volume":"8","author":"Swan","year":"2018","journal-title":"Clin. Pract."},{"key":"10.1016\/j.exer.2022.109342_bib44","doi-asserted-by":"crossref","DOI":"10.1007\/s13258-022-01260-x","article-title":"Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency","author":"Tang","year":"2022","journal-title":"Genes Genom."},{"key":"10.1016\/j.exer.2022.109342_bib45","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/bioinformatics\/btv098","article-title":"Sambamba: fast processing of NGS alignment formats","volume":"31","author":"Tarasov","year":"2015","journal-title":"Bioinformatics"},{"key":"10.1016\/j.exer.2022.109342_bib46","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/13816810.2017.1393831","article-title":"A new perspective on the genetics of keratoconus: why have we not been more successful?","volume":"39","author":"Valgaeren","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"10.1016\/j.exer.2022.109342_bib47","article-title":"Novel heterozygous missense variant in GRIA4 gene associated with neurodevelopmental disorder with or without seizures and gait abnormalities","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Genet."},{"key":"10.1016\/j.exer.2022.109342_bib48","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.exer.2022.109342_bib49","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1534\/g3.115.018564","article-title":"Exome sequencing: current and future perspectives","volume":"5","author":"Warr","year":"2015","journal-title":"G3 (Bethesda)"},{"key":"10.1016\/j.exer.2022.109342_bib50","article-title":"The microtubule-associated protein ASPM regulates spindle assembly and meiotic progression in mouse oocytes","volume":"7","author":"Xu","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2022.109342_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2021.145575","article-title":"The function and pathogenic mechanism of filamin A","volume":"784","author":"Zhou","year":"2021","journal-title":"Gene"}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522004237?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522004237?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:34:44Z","timestamp":1762148084000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483522004237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":52,"alternative-id":["S0014483522004237"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2022.109342","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Trio-based exome sequencing broaden the genetic spectrum in keratoconus","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2022.109342","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"109342"}}