{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:27:58Z","timestamp":1790015278466,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007543","name":"Grantov\u00e1 Agentura, Univerzita Karlova","doi-asserted-by":"publisher","award":["GAUK 165815"],"award-info":[{"award-number":["GAUK 165815"]}],"id":[{"id":"10.13039\/100007543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["17\u201030500A"],"award-info":[{"award-number":["17\u201030500A"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NV19\u201006\u201000189"],"award-info":[{"award-number":["NV19\u201006\u201000189"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["UHM 0064203\/9782"],"award-info":[{"award-number":["UHM 0064203\/9782"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the <jats:italic>COL2A1<\/jats:italic> or <jats:italic>COL11A1<\/jats:italic> genes. Using Sanger and next\u2010generation sequencing, 11 different <jats:italic>COL2A1<\/jats:italic> variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the <jats:italic>COL2A1<\/jats:italic> disease\u2010causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in <jats:italic>COL2A1<\/jats:italic> showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel <jats:italic>COL11A1<\/jats:italic> variants were found. The propositus with a de novo variant showed an ultrarare Marshall\/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with <jats:italic>COL2A1<\/jats:italic> or <jats:italic>COL11A1<\/jats:italic> variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.<\/jats:p>","DOI":"10.1111\/ahg.12386","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T20:08:25Z","timestamp":1589918905000},"page":"380-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Expanding the phenotype spectrum associated with pathogenic variants in the <i>COL2A1<\/i> and <i>COL11A1<\/i> genes"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-9103","authenticated-orcid":false,"given":"Jana","family":"\u010cop\u00edkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-5909","authenticated-orcid":false,"given":"Jana","family":"Pad\u011brov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-7205","authenticated-orcid":false,"given":"V\u011bra","family":"Rom\u00e1nkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-8484","authenticated-orcid":false,"given":"Mark\u00e9ta","family":"Havlovicov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-4759","authenticated-orcid":false,"given":"Miroslava","family":"Bala\u0161\u010d\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-0530","authenticated-orcid":false,"given":"Michaela","family":"Zelinov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-7840","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"Vejvalkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-757X","authenticated-orcid":false,"given":"Martina","family":"Simandlov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-2500","authenticated-orcid":false,"given":"Jana","family":"\u0160t\u011bp\u00e1nkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-1158","authenticated-orcid":false,"given":"V\u011bra","family":"Ho\u0159\u00ednov\u00e1","sequence":"additional","affiliation":[{"name":"Reprofit International  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6528-2235","authenticated-orcid":false,"given":"Eva","family":"Kantorov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Nemocnice \u010cesk\u00e9 Bud\u011bjovice  \u010cesk\u00e9 Bud\u011bjovice Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-5835","authenticated-orcid":false,"given":"Gabriela","family":"K\u0159e\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"GENNET  Liberec Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6020-1048","authenticated-orcid":false,"given":"Jana","family":"Posp\u00ed\u0161ilov\u00e1","sequence":"additional","affiliation":[{"name":"Molecular Biology AGEL Laboratories  Nov\u00fd Ji\u010d\u00edn Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-511X","authenticated-orcid":false,"given":"Arp\u00e1d","family":"Boday","sequence":"additional","affiliation":[{"name":"Molecular Biology AGEL Laboratories  Nov\u00fd Ji\u010d\u00edn Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-5142","authenticated-orcid":false,"given":"Anna Uhrov\u00e1","family":"Meszarosov\u00e1","sequence":"additional","affiliation":[{"name":"DNA Laboratory, Department of Child Neurology, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-3919","authenticated-orcid":false,"given":"Marek","family":"Turnovec","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-000X","authenticated-orcid":false,"given":"Pavel","family":"Vot\u00fdpka","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-8486","authenticated-orcid":false,"given":"Petra","family":"Li\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"},{"name":"Department of Ophthalmology, First Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4308-1595","authenticated-orcid":false,"given":"Radka","family":"Kreml\u00edkov\u00e1 Pourov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/302585"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22915"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0285-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsigen.2009.10.007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.035717"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.23"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2012.05.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","unstructured":"Karczewski K. J. Francioli L. C. Tiao G. Cummings B. B. Alf\u00f6ldi J. Wang Q. &MacArthur D. G.(2019).Variation across 141 456 human exomes and genomes reveals the spectrum of loss\u2010of\u2010function intolerance across human protein\u2010coding genes.https:\/\/doi.org\/10.1101\/531210","DOI":"10.1101\/531210"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36681"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.13"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200301000-00004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-0058-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19981102)80:2<115::AID-AJMG5>3.0.CO;2-O"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9497"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21257"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_22_1","volume-title":"GeneReviews\u00ae","author":"Robin N. H.","year":"2000"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30955"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"issue":"5","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/jmg.36.5.353","article-title":"Clinical and molecular genetics of Stickler syndrome","volume":"36","author":"Snead M. P.","year":"1999","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01959208"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.009"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9061"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/1066527041410418"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420316"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fahg.12386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.12386","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T15:34:48Z","timestamp":1693582488000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,19]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/ahg.12386"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12386","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,19]]},"assertion":[{"value":"2019-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}