{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:40:08Z","timestamp":1786527608085,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: To assess how historical patterns in retinitis pigmentosa (RP) gene inheritance, functional category, and phenotypic onset may inform the remaining unsolved RP discovery space. Methods: We manually reviewed PubMed-indexed primary reports in the RetiGene database, supplemented with PubMed-indexed human studies where necessary to improve extractable phenotype data. Gene-level variables extracted included age of symptom onset, inheritance pattern, functional category and syndromic association. Gene-level associations between earliest year of RP gene discovery and mean age of symptom onset were assessed, alongside temporal analyses for functional category, inheritance, and syndromic patterns. Results: Later year of gene discovery was associated with later mean age of symptom onset, both in the primary analysis restricted to genes with at least 5 extractable onset cases (n = 83, p &lt; 0.001) and in a stricter sensitivity analysis restricted to genes with at least 10 onset cases (n = 66, p = 0.00525). Year of discovery differed significantly across functional categories (p &lt; 0.001). No significant temporal association was observed for AR versus non-AR inheritance or syndromic status. Conclusions: This hypothesis-generating analysis suggests that observed patterns likely reflect a combination of biological detectability, study design, and publication dynamics rather than intrinsic gene\u2013phenotype relationships alone; within this context, future RP-solving efforts may benefit from greater attention to less obvious biological pathways (such as ciliary, transport, and metabolic categories), along with later-presenting or less conspicuous phenotypes.<\/jats:p>","DOI":"10.3390\/genes17080940","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:11:36Z","timestamp":1786525896000},"page":"940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Trajectory of Gene Discovery in Retinitis Pigmentosa"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0952-7713","authenticated-orcid":false,"given":"Anthony X. J.","family":"Wong","sequence":"first","affiliation":[{"name":"Ocular Genetics Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Chua","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6399-3877","authenticated-orcid":false,"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwee Goon","family":"Tay","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Quinodoz","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Mittlere Str. 91, 4031 Basel, Switzerland"},{"name":"Department of Ophthalmology, University of Basel, Mittlere Str. 91, 4056 Basel, Switzerland"},{"name":"Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9869-5159","authenticated-orcid":false,"given":"Tien-En","family":"Tan","sequence":"additional","affiliation":[{"name":"Ocular Genetics Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"},{"name":"Department of Surgical Retina, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-9950","authenticated-orcid":false,"given":"Carlo","family":"Rivolta","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel (IOB), Mittlere Str. 91, 4031 Basel, Switzerland"},{"name":"Department of Ophthalmology, University of Basel, Mittlere Str. 91, 4056 Basel, Switzerland"},{"name":"Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5356-7604","authenticated-orcid":false,"given":"Beau J.","family":"Fenner","sequence":"additional","affiliation":[{"name":"Ocular Genetics Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"},{"name":"Department of Medical Retina, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","first-page":"57","article-title":"The Diagnostic Yield of Next Generation Sequencing in Inherited Retinal Diseases: A Systematic Review and Meta-analysis","volume":"249","author":"Gocuk","year":"2023","journal-title":"Arch. 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