{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:01:51Z","timestamp":1780434111219,"version":"3.54.1"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["176097"],"award-info":[{"award-number":["176097"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["204285"],"award-info":[{"award-number":["204285"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017645","name":"Moorfields Eye Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017645","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Moorfields and UCL Institute of Ophthalmology Biomedical Research Centre"},{"name":"Ghent University Special Research Fund","award":["BOF20\/GOA\/023"],"award-info":[{"award-number":["BOF20\/GOA\/023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inherited retinal dystrophies (IRDs) are characterized by their high clinical and genetic heterogeneity. Despite significant advances in the identification of genes associated with IRDs, many individuals and families still have not received a definite molecular diagnosis. Here, we performed clinical examinations and conducted genetic testing in five families with IRD. Whole exome sequencing in the five index cases revealed a heterozygous missense variant, c.209G\u2009&amp;gt;\u2009A, p.(Gly70Glu) in the ARL3 gene (NM_004311.4). A de novo occurrence was demonstrated in one affected individual and autosomal dominant inheritance in nine affected individuals from four families. Their phenotypes displayed variable expressivity, and ranged from rod-cone to cone-rod dystrophy with photophobia. Human induced pluripotent stem cells (hiPSCs) were generated from dermal fibroblasts from the individual with the de novo ARL3 variant and were differentiated to retinal pigment epithelium cells (RPE) and retinal organoids. Immunofluorescence analyses in these models showed decreased INPP5E localization within the cilia of RPE and connecting cilia of retinal organoids, as well as reduced PDE6\u237a in the organoid outer segments, suggesting that the p.(Gly70Glu) variant causes IRD by defective lipidated protein transport in photoreceptors and\/or RPE. This is the first study of ARL3 dysfunction in human retinal cells, highlighting its importance for retinal homeostasis, as well as a variability in the clinical presentation of ARL3-associated IRD.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf029","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T23:27:51Z","timestamp":1741130871000},"page":"821-834","source":"Crossref","is-referenced-by-count":7,"title":["A novel recurrent <i>ARL3<\/i> variant c.209G\u2009&amp;gt;\u2009A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-4931","authenticated-orcid":false,"given":"Julio C","family":"Corral-Serrano","sequence":"first","affiliation":[{"name":"UCL Institute of Ophthalmology , EC1V 9EL London ,","place":["United 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,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology , EC1V 9EL London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Escher","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Van den Broeck","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Ghent , 9000 Ghent,","place":["Belgium"]},{"name":"Department of Head and Skin, University Ghent , 9000 Ghent,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cancellieri","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , 4031 Basel ,","place":["Switzerland"]},{"name":"Department of Ophthalmology, University of Basel , 4056 Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Toulis","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology , EC1V 9EL London ,","place":["United Kingdom"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Departament de Gen\u00e8tica, Microbiologia i Estad\u00edstica, Universitat de Barcelona , 08193 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Ghent , 9000 Ghent,","place":["Belgium"]},{"name":"Department of Head and Skin, University Ghent , 9000 Ghent,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"de Zaeytijd","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Ghent , 9000 Ghent,","place":["Belgium"]},{"name":"Department of Head and Skin, University Ghent , 9000 Ghent,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"You","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology , EC1V 9EL London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-7351","authenticated-orcid":false,"given":"Daniele","family":"Ottaviani","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology , EC1V 9EL London ,","place":["United 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