Understanding ABCA4 and predicting the future

Prof Andrew Webster, Moorfields Eye Hospital - £109,432

The ABCA4 gene is involved in a number of macular dystrophies, particularly Stargardt disease. Changes in the gene can lead to developing a macular dystrophy; however a lot of these changes are also seen in those without any sight loss. This work aims to understand why some people experience sight loss and others don’t, even with the same gene changes.

What is the problem?

ABCA4 is a large gene and mutations in it can lead to a number of macular dystrophies including Stargardt disease, Bulls eye maculopathy and cone-rod dystrophy. However, because the gene is so large and there are so many different variants (small changes in the gene) in the population, it is often difficult to understand which changes in the gene, or combination of changes, lead to macular disease. Many variants that are seen in people with vision loss are also found in people without vision loss, including siblings with the same variants but only one has a macular dystrophy. Therefore, it can be difficult to provide an accurate and correct genetic diagnosis.

What are they doing?

This project aims to compare the genetic variants of those without vision loss to those with vision loss, using large genetic datasets of the general population and those attending Moorfields Eye Hospital with a macular dystrophy. The researchers also want to find out why some people with certain ABCA4 variants will develop vision loss while others, with the same variants, will have completely normal vision.

How can this help?

Providing someone with a correct genetic diagnosis can provide more information about how the condition is likely to advance. It can also open up the possibility of taking part in future clinical trials, which will become more common as more gene therapies are created.

This work aims to understand and identify other factors involved in the cause of vision loss in those with the same ABCA4 variants, which could hopefully be used as a target for treatment.