RHO was first reported in relation to autosomal dominant retinitis pigmentosa in 1990 (Dryja et al., PMID: 2137202), RHO variants have also been reported as the cause of autosomal recessive retinitis pigmentosa (PMID: 7987385) and autosomal dominant congenital stationary night blindness (PMID: 8107847). Per criteria outlined by the ClinGen Lumping & Splitting Working Group, we found diverse molecular mechanisms underlying these disease entities, ranging from biallelic loss-of-function to monoallelic gain-of-function, but no significant phenotypic variability as well as some overlap in inheritance pattern among the different groups of affected patients. Therefore, retinitis pigmentosa 4 (MIM# 613731) and autosomal dominant congenital stationary night blindness 1 (MIM# 610445) have been lumped into a single curation, under the broad disease term RHO-related retinopathy.
This curation includes 6 variants (5 missense and 1 nonsense) that have been reported in 5 probands in 6 publications (PMIDs: 1302614, 2137202, 26202387, 7846071, 38111930, 31239368, 34635090). More evidence is available in the literature, but was not required for inclusion. The mechanism of pathogenicity is reported to be mainly gain-of-function or dominant negative, with a few cases being loss-of-function.
This gene-disease relationship is also supported by animal models, expression studies and in vitro functional assays (PMIDs: 38479725, 30976840, 17167410, 21126223, 30239781).
In summary, there is definitive evidence supporting the relationship between RHO and RHO-related retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time without the emergence of conflicting evidence. This classification was approved by the ClinGen Retina GCEP on January, 2nd, 2025 (SOP Version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.