{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:13:00Z","timestamp":1770919980484,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012247","name":"Program of Shanghai Academic Research Leader","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> The purpose of this study was to investigate the clinical and genetic characteristics of the retinitis pigmentosa GTPase regulatory factor gene (<jats:italic>RPGR<\/jats:italic>) in a Chinese cohort.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A retrospective analysis was performed on 80 subjects with <jats:italic>RPGR<\/jats:italic>-retinal dystrophy (<jats:italic>RPGR<\/jats:italic>-RD) for detailed genetic and clinical characterization. The panel-based next-generation sequencing of 792 causative genes involved in common genetic eye diseases was conducted in all individuals, followed by clinical variant interpretation. Information, including age, sex, geographic distribution, family history, consanguineous marriage, age at symptom onset, disease duration, best corrected visual acuity (BCVA), and complete ophthalmologic examination results, was collected.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> This cohort (41 men and 39 women) included 26 families (26 probands and their available family members) and 13 sporadic cases. The average age of these participants was 36.35 \u00b1 17.68\u00a0years, and the majority of the families were from eastern China (28 families, 71.79%). The average duration of disease in the probands was 22.68 \u00b1 15.80 years. In addition, the average BCVA values of the right and left eyes in the probands were 0.96 \u00b1 0.77 and 1.00 \u00b1 0.77, respectively. A total of 34 <jats:italic>RPGR<\/jats:italic> variants were identified, including 6 reported variants and 28 novel variants. Among these variants, NM_001034853.1: c.2899_2902delGAAG and c.2744_2745ins24 were considered <jats:italic>de novo<\/jats:italic> variants. The majority of the <jats:italic>RPGR<\/jats:italic> variants were classified as likely pathogenic, accounting for 70.59% of the variants (24 variants). The most common nucleotide and amino acid changes identified in this study were deletions (16 variants, 45.06%) and frameshifts (17 variants, 50.00%), respectively. Genetic analysis revealed that these <jats:italic>RPGR<\/jats:italic> variants were distributed in 10 different subregions of <jats:italic>RPGR,<\/jats:italic> and 70.59% of the <jats:italic>RPGR<\/jats:italic> variants (24 variants) were located in exon 15. Four <jats:italic>RPGR<\/jats:italic> variants, NM_001034853.1: c.2405_2406delAG, c.1345C &amp;gt; T, c.2218G &amp;gt; T and c.2236_2237delGA, occurred at a very high frequency of 28.21% (11 families) among 39 unrelated families.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study expands the known mutational spectrum of <jats:italic>RPGR<\/jats:italic>, and we provide a new reference for the genetic diagnosis of <jats:italic>RPGR<\/jats:italic> variants.<\/jats:p>","DOI":"10.3389\/fgene.2022.850122","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T12:14:33Z","timestamp":1648728873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutation Analysis of the RPGR Gene in a Chinese Cohort"],"prefix":"10.3389","volume":"13","author":[{"given":"Hong-Li","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Guan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan-Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Yuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge-Zhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"a017392","DOI":"10.1101\/cshperspect.a017392","article-title":"Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR","volume":"5","author":"Beltran","year":"2015","journal-title":"Cold Spring Harb Perspect. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1136\/bjo.59.4.177","article-title":"X-linked Retinitis Pigmentosa","volume":"59","author":"Bird","year":"1975","journal-title":"Br. J. Ophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1093\/hmg\/9.14.2085","article-title":"Identification of a Novel Protein Interacting with RPGR","volume":"9","author":"Boylan","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1086\/340848","article-title":"A Comprehensive Mutation Analysis of RP2 and RPGR in a North American Cohort of Families with X-Linked Retinitis Pigmentosa","volume":"70","author":"Breuer","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/ppul.22632","article-title":"RPGR Mutations Might Cause Reduced Orientation of Respiratory Cilia","volume":"48","author":"Bukowy-Biery\u0142\u0142o","year":"2013","journal-title":"Pediatr. Pulmonol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1001\/archopht.1948.00900030700009","article-title":"Choroidoretinal Degeneration","volume":"40","author":"Falls","year":"1948","journal-title":"Arch. Ophthalmol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1001\/archopht.1986.01050210083030","article-title":"X-linked Recessive Retinitis Pigmentosa","volume":"104","author":"Fishman","year":"1986","journal-title":"Arch. Ophthalmol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.ophtha.2019.04.038","article-title":"Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa","volume":"126","author":"Gao","year":"2019","journal-title":"Ophthalmology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1136\/bjophthalmol-2019-314679","article-title":"Mutation Spectrum of the Bestrophin-1 Gene in a Large Chinese Cohort with Bestrophinopathy","volume":"104","author":"Gao","year":"2019","journal-title":"Br. J. Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis Pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/13816810.2010.535889","article-title":"RPGR: Role in the Photoreceptor Cilium, Human Retinal Disease, and Gene Therapy","volume":"32","author":"Hosch","year":"2011","journal-title":"Ophthalmic Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3980\/j.issn.2222-3959.2014.05.02","article-title":"Genetic Analysis of Chinese Families Reveals a Novel Truncation Allele of the Retinitis Pigmentosa GTPase Regulator Gene","volume":"7","author":"Hu","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3389\/fgene.2019.00773","article-title":"ABCA4 Gene Screening in a Chinese Cohort with Stargardt Disease: Identification of 37 Novel Variants","volume":"10","author":"Hu","year":"2019","journal-title":"Front. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"44465","DOI":"10.1038\/srep44465","article-title":"Analysis of RP2 and RPGR Mutations in Five X-Linked Chinese Families with Retinitis Pigmentosa","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"B15","first-page":"1167","article-title":"Mutational Analysis of RPGR and RP2 Genes in Japanese Patients with Retinitis Pigmentosa: Identification of Four Mutations","volume":"12","author":"Jin","year":"2006","journal-title":"Mol. Vis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-4419-1399-9_13","article-title":"Multiprotein Complexes of Retinitis Pigmentosa GTPase Regulator (RPGR), a Ciliary Protein Mutated in X-Linked Retinitis Pigmentosa (XLRP)","volume":"664","author":"Khanna","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/978-3-319-75402-4_64","article-title":"More Than Meets the Eye: Current Understanding of RPGR Function","volume":"1074","author":"Khanna","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1093\/hmg\/8.8.1571","article-title":"RPGR Transcription Studies in Mouse and Human Tissues Reveal a Retina-specific Isoform that Is Disrupted in a Patient with X-Linked Retinitis Pigmentosa","volume":"8","author":"Kirschner","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/ng0596-35","article-title":"A Gene (RPGR) with Homology to the RCC1 Guanine Nucleotide Exchange Factor Is Mutated in X-Linked Retinitis Pigmentosa (RP3)","volume":"13","author":"Meindl","year":"1996","journal-title":"Nat. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/sj.ejhg.5200352","article-title":"Mutation Analysis of the RPGR Gene Reveals Novel Mutations in South European Patients with X-Linked Retinitis Pigmentosa","volume":"7","author":"Miano","year":"1999","journal-title":"Eur. J. Hum. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3591","DOI":"10.1093\/hmg\/ddq275","article-title":"Interaction of Retinitis Pigmentosa GTPase Regulator (RPGR) with RAB8A GTPase: Implications for Cilia Dysfunction and Photoreceptor Degeneration","volume":"19","author":"Murga-Zamalloa","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"240","DOI":"10.5301\/ejo.5000879","article-title":"Novel Variants of RPGR in X-Linked Retinitis Pigmentosa Families and Genotype-Phenotype Correlation","volume":"27","author":"Parmeggiani","year":"2017","journal-title":"Eur. J. Ophthalmol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3109\/13816818109036022","article-title":"Sex-difference in Progressive Cone Dystrophy. I","volume":"1","author":"Pinckers","year":"1981","journal-title":"Ophthalmic Paediatrics Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/hmg\/5.6.827","article-title":"Identification of a Gene Disrupted by a Microdeletion in a Patient with X-Linked Retinitis Pigmentosa (XLRP)","volume":"5","author":"Roepman","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1093\/hmg\/5.7.1035","article-title":"Positional Cloning of the Gene for X-Linked Retinitis Pigmentosa 3: Homology with the Guanine-Nucleotide-Exchange Factor RCC1","volume":"5","author":"Roepman","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1086\/379379","article-title":"RP2 and RPGR Mutations and Clinical Correlations in Patients with X-Linked Retinitis Pigmentosa","volume":"73","author":"Sharon","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/IAE.0000000000002125","article-title":"Clinical and Genetic Characteristics of Male Patients with Rpgr-Associated Retinal Dystrophies: A Long-Term Follow-Up Study","volume":"39","author":"Talib","year":"2018","journal-title":"Retina"},{"key":"B28","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/78182","article-title":"Mutational Hot Spot within a New RPGR Exon in X-Linked Retinitis Pigmentosa","volume":"25","author":"Vervoort","year":"2000","journal-title":"Nat. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1038\/s41433-020-01150-0","article-title":"A Novel Mutation of the RPGR Gene in a Chinese X-Linked Retinitis Pigmentosa Family and Possible Involvement of X-Chromosome Inactivation","volume":"35","author":"Wang","year":"2021","journal-title":"Eye"},{"key":"B30","doi-asserted-by":"publisher","first-page":"600210","DOI":"10.3389\/fgene.2021.600210","article-title":"Genotype-Phenotype Analysis of RPGR Variations: Reporting of 62 Chinese Families and a Literature Review","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.850122\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T12:14:41Z","timestamp":1648728881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.850122\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":30,"alternative-id":["10.3389\/fgene.2022.850122"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.850122","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]},"article-number":"850122"}}