PRPF31 was first reported in relation to an inherited retinal dystrophy, described as autosomal dominant retinitis pigmentosa (adRP), in 2001 (Vithana et al., PMID: 11545739). To account for a spectrum of retinal phenotypes that may be caused by variants in this gene, and in accordance with the ClinGen Lumping and Splitting guidelines, the disease entity used for this curation is PRPF31-related retinopathy. This condition is characterized by night blindness (onset in teens), progressive visual loss, and blindness (onset in 30s).
Ten variants (missense, in-frame indel, nonsense, frameshift, complex rearrangement) that have been reported in 10 probands in 06 publications (PMIDs: 11545739, 12714658, 12923864, 23288994, 29375987, 20939871) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. Interestingly, incomplete penetrance has been frequently observed in families with PRPF31 pathogenic variants. There are over 200 PRPF31 pathogenic and likely pathogenic variants listed on ClinVar (07/05/2022).
The mechanism of pathogenicity is reported to be LOF. This gene-disease relationship is also supported by functional studies in patient derived organoids and retinal pigment epithelium, and Prpf31+/- mouse (PMIDs: 30315276, 20811066).
In summary, PRPF31 is definitively associated with PRPF31-releated retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This clinical validity classification was approved by the ClinGen Retina GCEP on July 7, 2022 (SOP v9).
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.