Is there more than one gene behind Coats?
- Type of funding: PhD Studentship
- Grant Holder: Dr Carmel Toomes
- Institute: University of Leeds
- Region: North West
- Start date: November 2014
- End Date: April 2018
- Priority: Causes
- Eye Category:
Exudative retinitis, also known as Coats disease, is a rare, childhood blinding condition that usually affects one eye only. Blood vessels at the back of the eye do not develop normally, and become leaky.
Coats wasn’t thought of as a genetic condition as it doesn’t run in families. But one study in the 1990s did find a fault in a gene called NDP in one person with Coats. NDP is important for the eye to develop blood vessels. So if one gene is linked to Coats, perhaps there are others.
Now that newer technology makes it faster, easier and cheaper to look for lots of genes at once, the research team want to repeat the 90s experiment that found NDP and look for other genes too. The PhD student is studying DNA from donors with Coats, to look for any genetic faults, they proteins the genes produce, what they do and whether any genes found are linked to other conditions too.Results from the study will help us understand more about how blood vessels grow and develop in Coats as a step to developing treatment. Discovering new genes may also tell us whether and how Coats is inherited, which would provide important information for families to plan for the future.
Identifying and characterising the genes and proteins underlying Coats diseaseAbnormal blood vessel development is a key pathological process in a number of different eye disorders including retinopathy of prematurity (ROP), diabetic retinopathy and age related macular degeneration. Understanding the molecular mechanisms and pathways which underlie normal and abnormal blood vessel development is therefore of major clinical importance as this information will aid in the development of new therapies and treatments. This project aims to add to this knowledge by genetically investigating Coats disease, an idiopathic, non-hereditary retinal vasculopathy.
To date, only one study has genetically investigated Coats disease and this led to the identification of a somatic mutation in 1/9 Coats eyes in the gene encoding Norrin (NDP) (1), which plays a key role in the Norrin/β-catenin signalling pathway which controls retinal angiogenesis (2). This project aims to build on this initial study using the latest sequencing technology. Through a collaboration with Professor Alex Levin and Dr Carol Shields from the Wills Eye Hospital, the team has obtained enucleated eyes from eight Coats disease patients. The PhD student is extracting DNA from these eyes and performing whole exome sequencing to try and find new genes which underlie Coats disease.
The function of the proteins encoded by these genes is being investigated to try and deduce their role in retinal angiogenesis. Finally, the student is utilizing high-throughput sequencing methods to screen the new genes in cohorts of patients with similar diseases (eg FEVR, Coats+, ROP) to determine if it plays a role in other retinal vasculopathies.