Non-coding gene discovered to be a cause of blindness

New genetic causes of inherited blindness have been discovered that may offer answers to families with unexplained vision loss.

Retinitis pigmentosa (RP) is a genetic condition that causes progressive damage to the retina, causing a gradual loss of night and peripheral vision. Around two million people worldwide live with this condition, yet for 30-50 percent of patients the genetic cause is still unknown. Scientists have now revealed that changes in non-coding genes – those which encode RNAs but do not translate into proteins – can be linked to the disease.

'The changes that have been uncovered through this research could provide a genetic diagnosis for thousands of patients affected by genetic sight loss for the first time,' said Dr Jamie Ellingford, lead genomic data scientist at Genomics England, London.

The breakthrough began with the study of a single family in which several children developed severe vision loss. When routine genetic testing failed to find an explanation, researchers analysed the family's entire genomes and identified an unexpected genetic change outside traditional protein-coding regions. This discovery prompted an international effort to search for similar changes in over 4700 people with inherited RP whose genetic cause was unidentified.

Through large-scale analysis of whole genome sequencing data from the UK's National Genomic Research Library, among other sources, researchers detected disease-causing changes in two genes called RNU4-2 and RNU6. These genes are essential for RNA splicing and when this process is disrupted, retinal cells appear particularly sensitive, leading to progressive vision loss.

'We've learned that changes in these RNA genes can be just as impactful as changes in protein-coding genes,' said Dr Susanne Roosing, molecular geneticist at Radboud University Medical Centre in Nijmegen, the Netherlands, who led the research. 'This is fundamental knowledge that broadens our understanding of hereditary diseases.'

These discoveries have already provided clear genetic answers for 153 people from 67 families and could explain around 1.4 percent of previously unsolved RP cases.

'They now know the source of their blindness,' Dr Roosing explained. 'And they can make informed choices, such as using preimplantation genetic testing to prevent passing the condition to their children'.

The research, published in Nature Genetics, highlights the importance of examining the entire genome when searching for the causes of inherited diseases.