{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:28:09Z","timestamp":1782286089929,"version":"3.54.5"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100015613","name":"Centre Hospitalier Universitaire de Lille","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015613","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum. Genet."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>RPGR (Retinitis Pigmentosa GTPase Regulator<\/jats:italic>\n                    ) is the main gene involved in X-linked retinitis pigmentosa (RP) and up to 28% of sporadic RP. Pathogenic variants are mostly located in its retina-specific transcript,\n                    <jats:italic>RPGRorf15<\/jats:italic>\n                    , especially in the terminal exon named\n                    <jats:italic>open reading frame 15 (ORF15)<\/jats:italic>\n                    , which is a highly repeated region. Because of this complex sequence, first- and second-generation short-read sequencing are difficult, both for male patients and for affected and relative females, resulting in numerous unresolved cases. Long-read sequencing appears to be the most appropriate to counter this problem. Using Oxford Nanopore Technology sequencing, we analysed 194 patients with retinal dystrophy (RD) (142 men and 52 women) suspected to be either X-linked (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200942) or autosomal (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009152), and for whom first-line sequencing of 230 retinal dystrophy genes, including\n                    <jats:italic>RP2<\/jats:italic>\n                    and\n                    <jats:italic>RPGRex1-19<\/jats:italic>\n                    , was negative. Pathogenic\n                    <jats:italic>ORF15<\/jats:italic>\n                    variants were found in 27 patients (13.9%), 21 men and 6 women. Of the 42 XLRD patients, 15 were carriers (35.7%), nine men and six women, most of them had rod-cone dystrophy. Of the 152 patients with isolated RD, only 12 carried\n                    <jats:italic>ORF15<\/jats:italic>\n                    variants (7.9%),all male patients, most of them had cone-rod dystrophy (41.7%). We demonstrate the efficacy of this technology to diagnose male cases with a family history of X-linked RD, as well as sporadic cases clinically not suggestive of\n                    <jats:italic>ORF15<\/jats:italic>\n                    . We also show how easy it is to analyse female carriers or affected women. We expect that more heterozygous women with severe disease and no family history will be identified by this technique in the future.\n                  <\/jats:p>","DOI":"10.1007\/s00439-025-02807-0","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:17:00Z","timestamp":1770981420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RPGRorf15 nanopore long-read sequencing improves retinitis pigmentosa molecular diagnosis for men and women"],"prefix":"10.1007","volume":"145","author":[{"given":"Manon","family":"Fabard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Devos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs F.","family":"Poncet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pascal","family":"Meneboo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Figeac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Villenet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Drumare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Defoort-Dhellemmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Meunier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Zanlonghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Grunewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Huin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Lecigne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily","family":"Smirnov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-4124","authenticated-orcid":false,"given":"Claire-Marie","family":"Dhaenens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"2807_CR1","doi-asserted-by":"publisher","unstructured":"AyyagariR, Demirci FY, Liu J et al (2002) X-linked recessive atrophic macular degeneration from RPGR mutation. Genomics 80:166\u2013171. https:\/\/doi.org\/10.1006\/geno.2002.6815","DOI":"10.1006\/geno.2002.6815"},{"key":"2807_CR2","doi-asserted-by":"publisher","first-page":"8232","DOI":"10.1167\/iovs.12-11025","volume":"53","author":"K Branham","year":"2012","unstructured":"Branham K, Othman M, Brumm M et al (2012) Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Invest Ophthalmol Vis Sci 53:8232\u20138237. https:\/\/doi.org\/10.1167\/iovs.12-11025","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2807_CR3","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1086\/340848","volume":"70","author":"DK Breuer","year":"2002","unstructured":"Breuer DK, Yashar BM, Filippova E et al (2002) A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. Am J Hum Genet 70:1545\u20131554. https:\/\/doi.org\/10.1086\/340848","journal-title":"Am J Hum Genet"},{"key":"2807_CR4","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41591-020-0763-1","volume":"26","author":"J Cehajic-Kapetanovic","year":"2020","unstructured":"Cehajic-Kapetanovic J, Xue K, de la Martinez-Fernandez C et al (2020) Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med 26:354\u2013359. https:\/\/doi.org\/10.1038\/s41591-020-0763-1","journal-title":"Nat Med"},{"key":"2807_CR5","doi-asserted-by":"publisher","first-page":"100898","DOI":"10.1016\/j.preteyeres.2020.100898","volume":"82","author":"SR De Silva","year":"2021","unstructured":"De Silva SR, Arno G, Robson AG et al (2021) The X-linked retinopathies: physiological insights, pathogenic mechanisms, phenotypic features and novel therapies. Prog Retin Eye Res 82:100898. https:\/\/doi.org\/10.1016\/j.preteyeres.2020.100898","journal-title":"Prog Retin Eye Res"},{"key":"2807_CR6","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.oret.2019.11.010","volume":"4","author":"AT Fahim","year":"2020","unstructured":"Fahim AT, Sullivan LS, Bowne SJ et al (2020) X-Chromosome inactivation is a biomarker of clinical severity in female carriers of RPGR-Associated X-Linked retinitis pigmentosa. Ophthalmol Retina 4:510\u2013520. https:\/\/doi.org\/10.1016\/j.oret.2019.11.010","journal-title":"Ophthalmol Retina"},{"key":"2807_CR7","doi-asserted-by":"publisher","unstructured":"Garc\u00eda-HoyosM, Garcia-Sandoval B, Cantalapiedra D et al (2006) Mutational screening of the RP2 and RPGR genes in Spanish families with X-linked retinitis pigmentosa. 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Informed consent was obtained for each patient. The laboratory\u2019s DNA collection (Base-OPH) has been granted approval number DEC22-323, and the use of data from this database has been approved by the CNIL under number CNIL DR-2023-061.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"20"}}