{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:04Z","timestamp":1787028484440,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T00:00:00Z","timestamp":1662768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Precise genetic diagnosis in RPE65-mediated retinitis pigmentosa (RP) is necessary to establish eligibility for genetic treatment with voretigene neparvovec: a recombinant adeno-associated viral vector providing a functional RPE65 gene. This case report aims to report a novel RP-related point mutation RPE65 c.353G&gt;A, p.(Arg118Lys), a variant of uncertain significance associated with a severe clinical presentation and the striking phenotypic feature of complete macular atrophy. We report the case of a 40-year-old male with inherited retinal dystrophy, all features typical for the RPE65-associated RP, and marked macular atrophy. Genetic testing identified that the patient was a compound heterozygote in trans form with two heterozygous variants: RPE65 c.499G&gt;T, p.(Asp167Tyr) and RPE65 c.353G&gt;A, p.(Arg118Lys). Furthermore, short-wavelength and near-infrared autofluorescence patterns exhibited deficiencies specific to mutations in the visual cycle genes. To the best of our knowledge, RPE65 c.353G&gt;A, p.(Arg118Lys) is the first described point mutation on this locus, among all other reported insertional mutations, currently classified as likely benign and of uncertain significance. We concluded that this variant contributed to the pathological phenotype, demonstrating its significance clearly to be reclassified as likely pathogenic. This being the case, patients with this specific variant in homozygous or compound heterozygous form would be likely candidates for genetic treatment with voretigene neparvovec.<\/jats:p>","DOI":"10.3390\/ijms231810513","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["RPE65 c.353G&gt;A, p.(Arg118Lys): A Novel Point Mutation Associated with Retinitis Pigmentosa and Macular Atrophy"],"prefix":"10.3390","volume":"23","author":[{"given":"Mirjana","family":"Bjelo\u0161","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mladen","family":"Bu\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-4186","authenticated-orcid":false,"given":"Ana","family":"\u0106uri\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"\u0160ari\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damir","family":"Bosnar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Markovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Kuzmanovi\u0107 Elabjer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Rak","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital \u201cSveti Duh\u201d, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12413","DOI":"10.1073\/pnas.0503460102","article-title":"RPE65 is the isomerohydrolase in the retinoid visual 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