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 6/3/2020
UL https://doi.org/10.1167/iovs.16-19687