biostudies-literatureCorral-Serrano JCSwiss National Science FoundationNIHR Moorfields and UCL Institute of Ophthalmology Biomedical Research CentreMoorfields Eye CharityGhent University Special Research Fund821-834https://www.ebi.ac.uk/biostudies/studies/S-EPMC12010153biostudies-literatureUnknown34(9)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 > A, 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 pluriHuman molecular geneticsA novel recurrent ARL3 variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models.PMC12010153176097204285BOF20/GOA/023Leroy BPCoppieters FYou ZCorral-Serrano JCVaclavik VKaminska KEscher PVan de Sompele SCheetham MEVan den Broeck FJovanovic KToulis VDe Baere ERivolta CTran VHCancellieri Fde Zaeytijd JQuinodoz MBordeanu GOttaviani DHardcastle AJfalseA novel recurrent ARL3 variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models.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 > A, 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 pluri2025-01-01T00:00:00Z2025 Apr2026-06-01T12:53:49.434Z2025-07-03T03:05:01.787ZS-EPMC120101534003733410.1093/hmg/ddaf029