Searching for undiscovered genetic causes of primary congenital glaucoma

Brief plain language background 

Primary congenital glaucoma (PCG) is a severe form of raised pressure within the eye that develops in infancy and can cause blindness from a young age. PCG affects 1 in 10,000 children born in the UK but can occur as frequently as 1 in 1,250 births in certain populations. We know that PCG is caused by changes in our genetic code (known as mutations) and can affect siblings and children of patients with PCG.  

What problem/knowledge gap does it help address 

Less than 25% of patients with PCG currently receive a genetic diagnosis, so further work is needed to identify the genes involved. We will use a new approach that can read the entire genetic code in long sentences rather than a few words at a time, which is called long-read sequencing. This will help us find spelling mistakes or mutations in undiscovered genes that may cause PCG. This will help more families understand the cause of their glaucoma, improve our understanding of how the disease develops and provide potential targets to develop new treatments that could prevent sight loss.  

Aim of the project 

To identify novel genetic causes of PCG using a new approach called long-read sequencing. This is a pilot study which will sequence a smaller number of patients’ samples using this technique to decide whether it is beneficial to use this method in a larger study.  

Potential impact on people with sight loss 

By identifying new genetic causes of PCG and adding them to NHS genetic testing panels, we can bring benefit to families affected by PCG within 3 years. Increasing the number of families who receive a genetic diagnosis will enable more families to access accurate genetic counselling and family planning options. By improving our understanding of how the disease develops we can improve prognostication and individualised treatment for those affected. Over the next 10-15 years, the genes identified can form the basis for new treatments to reduce the severity of PCG and prevent or slow sight loss.