Advancing Diagnostics and Insights into PRPF31-Associated Retinitis Pigmentosa through Advanced Integrative Clinical, Genomics and Functional Approaches

Why is this research needed?

Retinitis pigmentosa (RP) is an inherited eye condition resulting from errors in genes affecting retinal function, ultimately leading to degeneration of retinal cells and gradual sight loss. PRPF31 is one of the genes responsible for RP. Occasionally, we encounter specific gene errors known as “non-coding variants” that potentially affect how the gene is edited or “spliced”. Understanding the true impact of these non-coding variants on gene splicing is challenging, and they often remain categorised as “variants of uncertain significance”. This leaves patients without a confirmed genetic diagnosis and uncertain about implications for their families. Additionally, we are yet to fully understand why some individuals with the same PRPF31 gene error develop RP while others do not.

What is the aim of the project?

The aim of this project is to improve diagnosis and understanding in RP caused by PRPF31 through two approaches. Firstly, the aim is to gain a better insight into the disease-causing potential of non-coding variants in PRPF31 and their impact on gene splicing. Secondly, the intention is to establish pathways for investigating the mechanisms that determine why some individuals with PRPF31 gene errors develop disease, while others do not.

Ultimately, this research aims to improve diagnostic accuracy and understanding of PRPF31-associated RP. Knowledge gained will provide better care and develop new treatments that will improve the lives of people with the condition.

How will this research help beat sight loss faster?

Ultimately, this study seeks to address missing heritability, and illuminate molecular mechanisms contributing to the variable penetrance observed in PRPF31-associated RP. Outcomes will improve genetic diagnosis, providing affected families with informed and personalised genetic counselling. Identifying genetic factors protective against development of disease can be leveraged for the development of new therapies. Results will be disseminated through publications, presentations and collaboration with an extensive clinical research network, benefitting PRPF31 patient cohorts globally.