RT Journal Article A1 Arno, Gavin A1 Hull, Sarah A1 Carss, Keren A1 Dev-Borman, Arundhati A1 Chakarova, Christina A1 Bujakowska, Kinga A1 van den Born, L. Ingeborgh A1 Robson, Anthony G. A1 Holder, Graham E. A1 Michaelides, Michel A1 Cremers, Frans P. M. A1 Pierce, Eric A1 Raymond, F. Lucy A1 Moore, Anthony T. A1 Webster, Andrew R. T1 Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1 JF Investigative Ophthalmology & Visual Science JO Invest. Ophthalmol. Vis. Sci. YR 2016 DO 10.1167/iovs.16-19687 VO 57 IS 11 SP 4806 OP 4813 SN 1552-5783 AB Mutation of RGR, encoding retinal G-protein coupled receptor was originally reported in association with retinal dystrophy in 1999. A single convincing recessive variant segregated perfectly in one family of five affected and two unaffected siblings. At least one further individual, homozygous for the same variant has since been reported. The aim of this report was to reevaluate the findings in consideration of data from a whole genome sequencing (WGS) study of a large cohort of retinal dystrophy families. Whole genome sequencing was performed on 599 unrelated probands with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography, fundus autofluorescence imaging (FAF) and spectral-domain optical coherence tomography (OCT). Overall we confirmed that affected individuals from six unrelated families were homozygous for both the reported RGR p.Ser66Arg variant and a nearby frameshifting deletion in CDHR1 (p.Ile841Serfs119*). All had generalized rod and cone dysfunction with severe macular involvement. An additional proband was heterozygous for the same CDHR1/RGR haplotype but also carried a second null CDHR1 mutation on a different haplotype. A comparison of the clinical presentation of the probands reported here with other CDHR1-related retinopathy patients shows the phenotypes to be similar in presentation, severity, and rod/cone involvement. These data suggest that the recessive retinal disorder previously reported to be due to homozygous mutation in RGR is, at least in part, due to variants in CDHR1 and that the true consequences of RGR knock-out on human retinal structure and function are yet to be determined. RD 4/13/2021 UL https://doi.org/10.1167/iovs.16-19687