Researchers from Radboud university medical center and the University of Basel have identified new genetic causes for inherited blindness, specifically retinitis pigmentosa (RP). The findings reveal that mutations in certain non-protein-coding RNA genes can lead to this eye condition, which affects approximately 1 in 5,000 people globally and often results in tunnel vision or legal blindness.
Retinitis pigmentosa is characterized by the gradual death of rod and cone cells in the retina. Individuals typically experience night blindness first, followed by tunnel vision, with some eventually losing their sight completely. While over a hundred genes have been linked to RP, between 30 and 50 percent of cases remain unexplained after standard DNA testing.
The research was initiated when an American family approached the team seeking answers about the cause of their inherited blindness and other genetic conditions. Lead researcher Susanne Roosing, molecular geneticist at Radboudumc, stated: "They came to us asking: what's behind this? Is there one cause explaining all these conditions, or are multiple genes involved?" After failing to find a known RP gene responsible through conventional analysis, researchers examined the entire DNA sequence of both parents and children. This approach clarified other conditions but not RP until they identified a variation in the RNU4-2 gene.
RNU4-2 is unique because it produces only RNA rather than proteins. This RNA forms complexes with proteins and other RNAs to help edit genetic information before protein synthesis occurs—a process known as splicing. Previous studies had linked changes in RNU4-2 to developmental disorders; however, the variant found in this family affected a critical hinge point in the RNA structure essential for retinal function.
Collaborating with Mathieu Quinodoz and Carlo Rivolta from the University of Basel as well as international colleagues, researchers analyzed DNA from 5,000 patients whose RP origins were still unknown. They discovered additional mutations not only in RNU4-2 but also four similar genes. These findings provided molecular diagnoses for 153 individuals across 67 families—explaining about 1.4 percent of previously unresolved global RP cases.
The American family who participated expressed satisfaction with these results. According to Roosing: "They now know the source of their blindness," adding that informed choices such as preimplantation genetic testing are now possible for them: "That's incredibly valuable."
Commenting on broader implications, Rodenburg said: "We've learned that changes in these RNA genes can be just as impactful as changes in protein-coding genes. This is fundamental knowledge that broadens our understanding of hereditary diseases."
