Mutations in CFI gene: which are harmless or harmful?

Professor David Kavanagh, Newcastle University - £104,176

This project investigated different mutations in the CFI gene to understand how they affect the risk of developing age-related macular degeneration (AMD). By identifying which mutations are harmful and how they affect the immune system, the research could help identify people who may benefit from targeted treatments.

What was the problem?

The CFI gene helps regulate part of the immune system called the complement system. Changes in this gene can affect how the complement system works, but not all mutations have the same effect. Some have been strongly linked to an increased risk of developing AMD, while others appear to be harmless.

Understanding what different mutations do is important because it could help researchers predict who is at greater risk of AMD and identify people who may benefit from treatments targeting the complement system.

What did the project achieve?

The team investigated 20 different mutations in the CFI gene and found that they affect the gene's activity in different ways. Some mutations resulted in insufficient levels of the CFI protein, while others produced a protein with an altered structure. Some mutations had no significant effect.

These differences help explain why people with mutations in the same gene can experience different effects. When a mutation affects the production or function of CFI, it can lead to over-activation of the complement system – part of the immune system that plays a role in the development of AMD.

The research also found considerable variation in how different mutations affected CFI, highlighting the complexity of how the gene is regulated.

What's next?

A better understanding of how individual CFI mutations affect the complement system could help researchers identify people who may benefit from complement-inhibiting treatments.

In the future, genetic screening could help identify specific CFI mutations and support the development of clinical trials or treatments targeted to individual mutations. This could contribute to more personalised approaches to treating AMD.