{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T03:04:25Z","timestamp":1765422265931,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health of the Czech Republic","award":["AZV NU20-07-00182"],"award-info":[{"award-number":["AZV NU20-07-00182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G&gt;A, c.[375_379del; 386A&gt;T], c.539C&gt;A and c.575_576insT were novel, all predicted to be null alleles. The c.539C&gt;A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.<\/jats:p>","DOI":"10.3390\/genes12111816","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T02:43:09Z","timestamp":1637289789000},"page":"1816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and Genetic Study of X-Linked Juvenile Retinoschisis in the Czech Population"],"prefix":"10.3390","volume":"12","author":[{"given":"Bohdan","family":"Kousal","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"},{"name":"Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Hlavata","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Vlaskova","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"Dvorakova","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Brichova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora","family":"Dubska","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Langrova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine in Hradec Kralove, Charles University and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea L.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lubica","family":"Dudakova","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Liskova","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"},{"name":"Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.preteyeres.2011.12.002","article-title":"X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms","volume":"31","author":"Molday","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1136\/bjo.79.7.697","article-title":"X linked retinoschisis","volume":"79","author":"George","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44060","DOI":"10.1038\/srep44060","article-title":"Genetic analysis and clinical features of X-linked retinoschisis in Chinese patients","volume":"7","author":"Hu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1136\/bjophthalmol-2017-310593","article-title":"Bullous X linked retinoschisis: Clinical features and prognosis","volume":"102","author":"Hinds","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1001\/archopht.1996.01100130270007","article-title":"Clinical features in affected males with X-linked retinoschisis","volume":"114","author":"George","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/BF00927256","article-title":"X-linked congenital retinoschisis","volume":"228","author":"Kellner","year":"1990","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_7","first-page":"487","article-title":"Clinical presentations of X-linked retinoschisis in Taiwanese patients confirmed with genetic sequencing","volume":"21","author":"Wang","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/bjo.85.2.238","article-title":"Different mutation of the XLRS1 gene causes juvenile retinoschisis with retinal white flecks","volume":"85","author":"Hotta","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1136\/bjophthalmol-2016-310110","article-title":"Peripheral fundus findings in X-linked retinoschisis","volume":"101","author":"Fahim","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/00006982-200507000-00012","article-title":"Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis","volume":"25","author":"Apushkin","year":"2005","journal-title":"Retina"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1136\/jmg.2004.029769","article-title":"X-linked retinoschisis: Clinical phenotype and RS1 genotype in 86 UK patients","volume":"42","author":"Pimenides","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/eye.2011.91","article-title":"X-linked retinoschisis maculopathy treated with topical dorzolamide, and relationship to genotype","volume":"25","author":"Khandhadia","year":"2011","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3109\/13816810.2013.779383","article-title":"Resolution of mid-peripheral schisis in x-linked retinoschisis with the use of dorzolamide","volume":"35","author":"Collison","year":"2014","journal-title":"Ophthalmic Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1097\/IAE.0b013e3181e587f9","article-title":"The use of carbonic anhydrase inhibitors in the retreatment of cystic macular lesions in retinitis pigmentosa and X-linked retinoschisis","volume":"31","author":"Thobani","year":"2011","journal-title":"Retina"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/ng1097-164","article-title":"Positional cloning of the gene associated with X-linked juvenile retinoschisis","volume":"17","author":"Sauer","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_16","first-page":"932","article-title":"First molecular evidence for a de novo mutation in RS1 (XLRS1) associated with X linked juvenile retinoschisis","volume":"36","author":"Gehrig","year":"1999","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1016\/S0042-6989(01)00188-2","article-title":"Analysis of photoreceptor function and inner retinal activity in juvenile X-linked retinoschisis","volume":"41","author":"Khan","year":"2001","journal-title":"Vision Res."},{"key":"ref_18","first-page":"816","article-title":"Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells","volume":"42","author":"Molday","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiao, S., Sun, W., Xiao, X., Li, S., Luo, H., Jia, X., Ouyang, J., Li, X., Wang, Y., and Jiang, Y. (2021). Clinical and genetic features of retinoschisis in 120 families with RS1 mutations. Br. J. Ophthalmol.","DOI":"10.1136\/bjophthalmol-2021-319668"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3109\/08820538.2013.825299","article-title":"X-linked juvenile retinoschisis (XLRS): A review of genotype-phenotype relationships","volume":"28","author":"Kim","year":"2013","journal-title":"Semin. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10633-014-9473-7","article-title":"ISCEV Standard for full-field clinical electroretinography (2015 update)","volume":"130","author":"McCulloch","year":"2015","journal-title":"Doc. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3892\/ijmm.2012.882","article-title":"Novel RS1 mutations associated with X-linked juvenile retinoschisis","volume":"29","author":"Yi","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","unstructured":"The Retinoschisis Consortium (1998). Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis. Hum. Mol. Genet., 7, 1185\u20131192.","DOI":"10.1093\/hmg\/7.7.1185"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1421","DOI":"10.1002\/mgg3.1421","article-title":"Clinical manifestation and genetic analysis in Chinese early onset X-linked retinoschisis","volume":"8","author":"Huang","year":"2020","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_27","first-page":"142","article-title":"Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene","volume":"103","author":"Hotta","year":"1998","journal-title":"Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/(SICI)1098-1004(199911)14:5<423::AID-HUMU8>3.0.CO;2-D","article-title":"Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change","volume":"14","author":"Hiriyanna","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_29","first-page":"833","article-title":"Molecular genetic characteristics of X-linked retinoschisis in Koreans","volume":"15","author":"Kim","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1167\/iovs.09-3418","article-title":"Correlation of genetic and clinical findings in Spanish patients with X-linked juvenile retinoschisis","volume":"50","author":"Cantalapiedra","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/(SICI)1098-1004(1999)13:4<338::AID-HUMU16>3.0.CO;2-0","article-title":"Identification of four novel mutations of the XLRS1 gene in Japanese patients with X-linked juvenile retinoschisis. Mutation in brief no. 234. Online","volume":"13","author":"Mashima","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1001\/archopht.118.1.93","article-title":"X-linked retinoschisis with point mutations in the XLRS1 gene","volume":"118","author":"Inoue","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45952","DOI":"10.1074\/jbc.M104360200","article-title":"Mapping of epitopes in discoidin domain receptor 1 critical for collagen binding","volume":"276","author":"Curat","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1093\/hmg\/11.24.3097","article-title":"Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis","volume":"11","author":"Wang","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1038\/eye.2008.358","article-title":"An unusual fundus phenotype of inner retinal sheen in X-linked retinoschisis","volume":"23","author":"Robson","year":"2009","journal-title":"Eye"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1167\/iovs.09-3839","article-title":"Null retinoschisin-protein expression from an RS1 c354del1-ins18 mutation causing progressive and severe XLRS in a cross-sectional family study","volume":"50","author":"Vijayasarathy","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3109\/13816810.2010.482555","article-title":"Long-term 12 year follow-up of X-linked congenital retinoschisis","volume":"31","author":"Vijayasarathy","year":"2010","journal-title":"Ophthalmic. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1167\/iovs.15-18354","article-title":"Structure\/Psychophysical Relationships in X-Linked Retinoschisis","volume":"57","author":"Bennett","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","first-page":"329","article-title":"Segmented swept source optical coherence tomography angiography assessment of the perifoveal vasculature in patients with X-linked juvenile retinoschisis: A serial case report","volume":"10","author":"Stringa","year":"2017","journal-title":"Int. Med. Case. Rep. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/eye.2017.281","article-title":"Swept-source and optical coherence tomography angiography in patients with X-linked retinoschisis","volume":"32","author":"Arias","year":"2018","journal-title":"Eye"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.3928\/23258160-20180907-03","article-title":"Optical Coherence Tomography Angiography Findings in X-Linked Retinoschisis","volume":"49","author":"Mastropasqua","year":"2018","journal-title":"Ophthalmic Surg. Lasers Imaging Retina"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.oret.2018.09.006","article-title":"Wide-Field Swept-Source OCT and Angiography in X-Linked Retinoschisis","volume":"3","author":"Han","year":"2019","journal-title":"Ophthalmol. Retina"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:32:22Z","timestamp":1760167942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["genes12111816"],"URL":"https:\/\/doi.org\/10.3390\/genes12111816","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2021,11,18]]}}}