A recent study has uncovered mutations in non-coding RNA as a new cause of retinitis pigmentosa (RP), a genetic eye disorder affecting approximately one in 5,000 people globally. The disorder typically starts with night blindness in youth and progresses to tunnel vision as the photoreceptor cells in the retina deteriorate, potentially leading to complete blindness. Despite over a hundred genes being linked to RP, around 30 to 40 percent of patients remain without a clear genetic diagnosis, leaving many families in prolonged uncertainty regarding their inherited vision loss.
Researchers at the Institute of Molecular and Clinical Ophthalmology Basel (IOB), collaborating with more than 100 institutions worldwide, have analyzed genetic data from nearly 5,000 individuals across 62 families affected by RP. Their findings indicate that the genetic alterations responsible for the condition are not located within protein-coding genes. Instead, in 153 patients, the researchers identified mutations in RNA molecules critical for the cell’s splicing machinery, which is responsible for editing genetic information prior to protein synthesis.
Significant Discoveries in Non-Coding RNA
The study identified mutations in five non-coding RNA genes: RNU4-2, RNU6-1, RNU6-2, RNU6-8, and RNU6-9. These genes produce RNA molecules instead of proteins, representing a previously unexplored area in the search for inherited blindness. The identified variants include both inherited and spontaneous mutations, with some passed down through generations while others emerged in affected individuals for the first time. Notably, all variants cluster in a critical region where the U4 and U6 RNA molecules, encoded by the RNU4 and RNU6 genes, interact. This interaction is essential for multiple proteins involved in RNA splicing.
The discovery also highlights the complexity of genetic disorders. While certain variants in RNU4-2 have been associated with neurodevelopmental disorders, those identified in this study specifically impact the retina. This finding resolves a long-standing question in the field; although mutations in proteins involved in RNA splicing, such as PRPF3, PRPF8, and PRPF31, have been linked to RP, this research demonstrates that the RNA molecules involved in the same cellular process can also lead to the disease.
Impact on Families and Future Research
For the families involved in this study, the implications are significant. The identified variants account for up to 1.4% of previously undiagnosed RP cases, allowing dozens of families worldwide to receive precise molecular diagnoses. This breakthrough enables access to genetic counseling, informed family planning decisions, and positioning for future treatments as they become available.
Moreover, this research marks an important advancement in the understanding of hereditary blindness. By expanding the focus beyond protein-coding genes into overlooked regions of the genome, researchers are broadening the diagnostic landscape. As genetic testing continues to evolve and RNA-based therapies advance, these findings provide crucial groundwork for identifying more patients with RP and developing treatments for a condition that currently lacks a cure.
The study by Quinodoz et al. is published in Nature Genetics (2026). The insights gained may pave the way for future research and therapeutic strategies in the realm of genetic eye disorders, reshaping the diagnostic and treatment landscape for affected individuals. For more information, the study can be accessed at: https://www.nature.com/articles/s41588-025-02451-4.
