{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:49:56Z","timestamp":1776001796018,"version":"3.50.1"},"reference-count":46,"publisher":"Life Science Alliance, LLC","issue":"10","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Research Training Group 1885"],"award-info":[{"award-number":["Research Training Group 1885"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>Progressive degeneration of rod and cone photoreceptors frequently is caused by mutations in the X-chromosomal gene Retinitis Pigmentosa GTPase Regulator (<jats:italic>RPGR<\/jats:italic>). Males hemizygous for a<jats:italic>RPGR<\/jats:italic>mutation often are affected by Retinitis Pigmentosa (RP), whereas female mutation carriers only occasionally present with severe RP phenotypes. The underlying pathomechanism leading to RP in female carriers is not well understood. Here, we analyzed a three-generation family in which two of three female carriers of a nonsense<jats:italic>RPGR<\/jats:italic>mutation presented with RP. Among two cell lines derived from the same female family members, differences were detected in<jats:italic>RPGR<\/jats:italic>transcript expression, in localization of RPGR along cilia, as well as in primary cilium length. Significantly, these differences correlated with alterations in X-chromosomal inactivation patterns found in the patient-derived cell lines from females. In summary, our data suggest that skewed X-chromosomal inactivation is an important factor that determines the disease manifestation of RP among female carriers of pathogenic sequence alterations in the<jats:italic>RPGR<\/jats:italic>gene.<\/jats:p>","DOI":"10.26508\/lsa.202201814","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T15:52:53Z","timestamp":1691596373000},"page":"e202201814","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Skewed X-inactivation is associated with retinal dystrophy in female carriers of<i>RPGR<\/i>mutations"],"prefix":"10.26508","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2202-528X","authenticated-orcid":true,"given":"Muhammad","family":"Usman","sequence":"first","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-4824","authenticated-orcid":true,"given":"Christoph","family":"J\u00fcschke","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Song","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Kastrati","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Owczarek-Lipska","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"},{"name":"Junior Research Group, Genetics of Childhood Brain Malformations, School of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jannis","family":"Eilers","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurenz","family":"Pauleikhoff","sequence":"additional","affiliation":[{"name":"Eye Center, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Lange","sequence":"additional","affiliation":[{"name":"Eye Center, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany"},{"name":"Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-8394","authenticated-orcid":true,"given":"John","family":"Neidhardt","sequence":"additional","affiliation":[{"name":"Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg, Oldenburg, Germany"},{"name":"Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"12380","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"2023100207250714000_6.10.e202201814.1","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2023100207250714000_6.10.e202201814.2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31642"},{"key":"2023100207250714000_6.10.e202201814.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2011.05.003"},{"key":"2023100207250714000_6.10.e202201814.4","doi-asserted-by":"publisher","DOI":"10.3928\/23258160-20220311-01"},{"key":"2023100207250714000_6.10.e202201814.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195677"},{"key":"2023100207250714000_6.10.e202201814.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0763-1"},{"key":"2023100207250714000_6.10.e202201814.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1007-8"},{"key":"2023100207250714000_6.10.e202201814.8","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2014.128"},{"key":"2023100207250714000_6.10.e202201814.9","doi-asserted-by":"publisher","DOI":"10.1002\/0470092645.ch3"},{"key":"2023100207250714000_6.10.e202201814.10","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.2.151"},{"key":"2023100207250714000_6.10.e202201814.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103194"},{"key":"2023100207250714000_6.10.e202201814.12","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12364"},{"key":"2023100207250714000_6.10.e202201814.13","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-17121-0_43"},{"key":"2023100207250714000_6.10.e202201814.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2019.11.010"},{"key":"2023100207250714000_6.10.e202201814.15","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.7"},{"key":"2023100207250714000_6.10.e202201814.16","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31854"},{"key":"2023100207250714000_6.10.e202201814.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"2023100207250714000_6.10.e202201814.18","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-020-09812-w"},{"key":"2023100207250714000_6.10.e202201814.19","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-1206"},{"key":"2023100207250714000_6.10.e202201814.20","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31984"},{"key":"2023100207250714000_6.10.e202201814.21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh092"},{"key":"2023100207250714000_6.10.e202201814.22","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30052"},{"key":"2023100207250714000_6.10.e202201814.23","doi-asserted-by":"publisher","DOI":"10.1080\/080352502762458030"},{"key":"2023100207250714000_6.10.e202201814.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103714"},{"key":"2023100207250714000_6.10.e202201814.25","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-35"},{"key":"2023100207250714000_6.10.e202201814.26","doi-asserted-by":"publisher","DOI":"10.3390\/genes9120643"},{"key":"2023100207250714000_6.10.e202201814.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00012-1"},{"key":"2023100207250714000_6.10.e202201814.28","first-page":"989","article-title":"Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females","volume":"54","author":"Pegoraro","year":"1994","journal-title":"Am J Hum Genet"},{"key":"2023100207250714000_6.10.e202201814.29","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20417"},{"key":"2023100207250714000_6.10.e202201814.30","unstructured":"RetNet\u2122 (2022) RetNet: The retinal information network. Available at: https:\/\/sph.uth.edu\/retnet\/. Accessed on 23 Mar 2023."},{"key":"2023100207250714000_6.10.e202201814.31","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-022-09872-0"},{"key":"2023100207250714000_6.10.e202201814.32","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.14.2095"},{"key":"2023100207250714000_6.10.e202201814.33","doi-asserted-by":"publisher","DOI":"10.1159\/000503687"},{"key":"2023100207250714000_6.10.e202201814.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.04.008"},{"key":"2023100207250714000_6.10.e202201814.35","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2015-307698"},{"key":"2023100207250714000_6.10.e202201814.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.05.003"},{"key":"2023100207250714000_6.10.e202201814.37","doi-asserted-by":"publisher","DOI":"10.1038\/78182"},{"key":"2023100207250714000_6.10.e202201814.38","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01981-8"},{"key":"2023100207250714000_6.10.e202201814.39","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb2803s71"},{"key":"2023100207250714000_6.10.e202201814.40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228418"},{"key":"2023100207250714000_6.10.e202201814.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-020-01150-0"},{"key":"2023100207250714000_6.10.e202201814.42","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7470"},{"key":"2023100207250714000_6.10.e202201814.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48385-w"},{"key":"2023100207250714000_6.10.e202201814.44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817639116"},{"key":"2023100207250714000_6.10.e202201814.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2020.11.023"},{"key":"2023100207250714000_6.10.e202201814.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13340-w"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202201814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:07:58Z","timestamp":1704895678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202201814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,8,4]]},"published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.26508\/lsa.202201814"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202201814","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]}}}