{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:14:02Z","timestamp":1790475242056,"version":"4.1.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold><jats:italic>RPGRIP1<\/jats:italic> encodes a ciliary protein expressed in the photoreceptor connecting cilium. Mutations in this gene cause \u223c5% of Leber congenital amaurosis (LCA) worldwide, but are also associated with cone\u2013rod dystrophy (CRD) and retinitis pigmentosa (RP) phenotypes. Our purpose was to clinically characterize <jats:italic>RPGRIP1<\/jats:italic> patients from our cohort, collect clinical data of additional <jats:italic>RPGRIP1<\/jats:italic> patients reported previously in the literature, identify common clinical features, and seek genotype\u2013phenotype correlations.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Clinical data were collected from 16 patients of our cohort and 212 previously reported <jats:italic>RPGRIP1<\/jats:italic> patients and included (when available) family history, best corrected visual acuity (BCVA), refraction, comprehensive ocular examination, optical coherence tomography (OCT) imaging, visual fields (VF), and full-field electroretinography (ffERG).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Out of 228 patients, the majority (197, 86%) were diagnosed with LCA, 18 (7%) with RP, and 13 (5%) with CRD. Age of onset was during early childhood (<jats:italic>n<\/jats:italic> = 133, average of 1.7 years). All patients but 6 had moderate hyperopia (<jats:italic>n<\/jats:italic> = 59, mean of 4.8D), and average BCVA was 0.06 Snellen (<jats:italic>n<\/jats:italic> = 124; only 10 patients had visual acuity [VA] &amp;gt; 0.10 Snellen). On funduscopy, narrowing of blood vessels was noted early in life. Most patients had mild bone spicule-like pigmentation starting in the midperiphery and later encroaching upon the posterior pole. OCT showed thinning of the outer nuclear layer (ONL), while cystoid changes and edema were relatively rare. VF were usually very constricted from early on. ffERG responses were non-detectable in the vast majority of cases. Most of the mutations are predicted to be null (363 alleles), and 93 alleles harbored missense mutations. Missense mutations were identified only in two regions: the RPGR-interacting domain and the C2 domains. Biallelic null mutations are mostly associated with a severe form of the disease, whereas biallelic missense mutations usually cause a milder disease (mostly CRD).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our results indicate that <jats:italic>RPGRIP1<\/jats:italic> biallelic mutations usually cause severe retinal degeneration at an early age with a cone\u2013rod pattern. However, most of the patients exhibit preservation of some (usually low) BCVA for a long period and can potentially benefit from gene therapy. Missense changes appear only in the conserved domains and are associated with a milder phenotype.<\/jats:p>","DOI":"10.3389\/fcell.2021.746781","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T06:40:28Z","timestamp":1634193628000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Retinal Degeneration Associated With RPGRIP1: A Review of Natural History, Mutation Spectrum, and Genotype\u2013Phenotype Correlation in 228 Patients"],"prefix":"10.3389","volume":"9","author":[{"given":"Avigail","family":"Beryozkin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamzah","family":"Aweidah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roque Daniel","family":"Carrero Valenzuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Iguzquiza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans P. 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