{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:13:31Z","timestamp":1789622011981,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000262","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["CD\u2010CMM\u20100224\u20100873\u2010HSC"],"award-info":[{"award-number":["CD\u2010CMM\u20100224\u20100873\u2010HSC"]}],"id":[{"id":"10.13039\/501100000262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Retinol dehydrogenases (RDHs) catalyze multiple steps in the visual cycle to regenerate 11\u2010cis\u2010retinal, a critical component in rod phototransduction. The structural homology between RDHs enables functional redundancy; yet Mendelian disorders are linked to RDHs. Variants in\n RDH12<\/jats:italic>\n and\n RDH5<\/jats:italic>\n cause non\u2010syndromic inherited retinal dystrophy (IRD), whilst variants in\n RDH11<\/jats:italic>\n cause syndromic IRD.\n RDH11<\/jats:italic>\n is a minor isoenzyme catalyzing two reactions: (i) reduction of all\u2010trans\u2010retinal in rod photoreceptors alongside\n RDH12<\/jats:italic>\n and\n RDH8<\/jats:italic>\n , and (ii) oxidation of 11\u2010cis\u2010retinol in the retinal pigment epithelium (RPE) alongside\n RDH5<\/jats:italic>\n and\n RDH10<\/jats:italic>\n . Prior cases with\n RDH11<\/jats:italic>\n demonstrated a generalized photoreceptor dystrophy, similar to\n RDH12<\/jats:italic>\n \u2010retinopathy. We describe a visually asymptomatic 7\u2010year\u2010old boy carrying a homozygous null variant in\n RDH11<\/jats:italic>\n [NM_016026.4:c.216C>A:p.(Cys72*)] with autism, dysmorphic features, oligodontia, microcephaly and a novel IRD. This retinopathy consisted of yellow deposits and hyperpigmentation within the RPE with absent autofluorescence and a normal electroretinogram implying sub\u2010optimal oxidation of 11\u2010cis\u2010retinol. These features are reminiscent of\n RDH5\u2010<\/jats:italic>\n retinopathy but milder. We termed this phenotype Retinal pigment Epitheliopathy due to Sub\u2010Optimal Recycling of Vitamin A (RESORVA). We propose that the divergence in retinal phenotypes among\n RDH11<\/jats:italic>\n cases is likely due to variant\u2010specific protein effects on paralogous gene functioning, such as differences in activation of transcriptional adaptation.\n <\/jats:p>","DOI":"10.1111\/cge.70128","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:35:43Z","timestamp":1767004543000},"page":"972-977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Retinal Pigment Epitheliopathy due to Sub\u2010Optimal Recycling of Vitamin A (\n RESORVA<\/scp>\n ): A Novel\n \n RDH11<\/i>\n <\/scp>\n \u2010Related Phenotype"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7462-7725","authenticated-orcid":false,"given":"Kirk A. J.","family":"Stephenson","sequence":"first","affiliation":[{"name":"Ophthalmology and Vision Sciences The Hospital for Sick Children (HSC) Toronto Ontario Canada"},{"name":"Ophthalmology and Vision Sciences University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Shao","sequence":"additional","affiliation":[{"name":"Genetics Program, North York General Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupreet","family":"Tumber","sequence":"additional","affiliation":[{"name":"Ophthalmology and Vision Sciences The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Tavares","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Higginbotham","sequence":"additional","affiliation":[{"name":"Division of Genome Diagnostics, Department of Pediatric Laboratory Medicine The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian R.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Division of Genome Diagnostics, Department of Pediatric Laboratory Medicine The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.","family":"Maynes","sequence":"additional","affiliation":[{"name":"Anesthesia and Pain Medicine and Program in Molecular Medicine The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammaji","family":"Rajala","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju V. S.","family":"Rajala","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"H\u00e9on","sequence":"additional","affiliation":[{"name":"Ophthalmology and Vision Sciences The Hospital for Sick Children (HSC) Toronto Ontario Canada"},{"name":"Ophthalmology and Vision Sciences University of Toronto Toronto Ontario Canada"},{"name":"Genetics and Genome Biology The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajoy","family":"Vincent","sequence":"additional","affiliation":[{"name":"Ophthalmology and Vision Sciences The Hospital for Sick Children (HSC) Toronto Ontario Canada"},{"name":"Ophthalmology and Vision Sciences University of Toronto Toronto Ontario Canada"},{"name":"Genetics and Genome Biology The Hospital for Sick Children (HSC) Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi800905v"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab316"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10100779"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8110746"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu291"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14108"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413172200"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(02)00204-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1207"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707477104"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208882200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081659"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1064-z"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70128","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:23:53Z","timestamp":1775802233000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/cge.70128"],"URL":"https:\/\/doi.org\/10.1111\/cge.70128","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]},"assertion":[{"value":"2025-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}