Non-coding, but not non-important: the hidden genes behind retinitis pigmentosa
A new study by researchers from Radboud University Medical Centre and the University of Basel has uncovered new genetic causes of Retinitis Pigmentosa (RP) that were once overlooked.
What happens in RP?
RP is one of the most common types of inherited retinal disease (IRD) affecting around 1 in 4,000 people globally. RP causes progressive vision loss, starting peripherally, due to the loss of light-sensing photoreceptor cells in the retina. There are two types of photoreceptors, cones and rods, which differ in structure, function and location. Rods are located in the periphery of the retina and are responsible for night vision and peripheral awareness. Cones are located in the centre of the retina and give you sharp vision and colour detection in good lighting. To learn more, please watch this short animation video on Inherited Retinal Disease.
What causes RP?
More than 100 genes have been identified as known causes of RP and a genetic test can reveal which one is responsible for a particular individual’s sight loss. This genetic diagnosis can provide valuable information for an individual, their family and their doctor. For around one third of people with inherited sight loss however, genetic testing won’t return a conclusive result, which can be extremely disappointing. This is because scientists haven’t yet clearly identified all of the genetic changes that can cause disease.
This latest research could help to explain why some people have previously had no identifiable genetic cause, potentially improving the overall understanding of inherited sight loss and diagnosis process.
The study:
It has long been established that mutations in genes that are responsible for encoding proteins in the retina can cause IRDs. You can find out more about this in our short animation video on genes and mutations here.
However, the DNA in our genetic code includes lots of sections that don’t provide the instructions for building proteins. Some of these sections are used to create special RNA that forms part of the cell’s machinery for editing genetic code during protein production. This editing process, also known as splicing, cuts out any irrelevant information and stitches together the important sections that make the information clear and readable for protein building to occur.
This study has shown that changes to one of these RNA-generating sections, known as RNU4-2, can cause RP. The mutations in RNU4-2 lead to faults in the editing machinery, which disrupts the editing process and can contribute to incorrect splicing of protein-coding genes. This results in jumbled building instructions and proteins that don’t work, ultimately leading to retinal damage.
Following this finding from 1 American family, researchers launched a global large-scale DNA analysis study involving 5,000 participants with an unknown genetic cause of RP. In addition to changes in the RNU4-2 gene, they found 4 similar genes, providing a genetic diagnosis for 153 individuals from 67 families. The original family is delighted that research on their genetic code has helped so many others.
These findings have significant implications for IRD research, genetic testing and diagnosis, potentially helping more families to get answers and transforming research towards treatment. The results also show that the IRD landscape is continuously evolving, highlighting the benefits for our community in keeping an up-to-date clinical picture of their eyes, having regular check-ups with an optician and engaging with the research news area of our website. However, it will take a little while for the new findings to make their way into diagnostic genetic tests, as further validation studies will be required.
If you are curious about genetic testing, you can head to the Unlock Genetics section on our website which hopes to empower people to make fully informed decisions about their lives, healthcare and family planning.