Investigating a FLCN-related disorder

We are funding a project looking at what happens if you are born with both copies of the FLCN gene not functioning properly. Find out more about the research from project lead Dr Fulya Taylan from Karolinska Institute, Stockholm, Sweden.

Some diseases are very rare and can affect just one person or a small group of people worldwide. BHD is one of these diseases. It makes people more likely to get certain types of cancer and can cause other problems like lung cysts and skin bumps in adulthood.

We have approximately 20 000 genes and most of them are found in two copies, including a gene called Folliculin (FLCN). In individuals with BHD, one of the copies of the FLCN gene is missing or not functioning properly. We, on the other side, want to know if there is a new disease where both copies of the FLCN gene are not functioning properly, and this is what we are investigating in our project.

A young male patient with an unknown syndrome came to our attention. He presented mainly problems with his immune system, learning difficulties, and developmental delay. He also developed leukemia at age 1 year. We analysed his entire genome and identified a very rare variant in both copies of the FLCN gene. Both his parents have one copy of the gene with this rare variant, but they don’t have the same problems as their son and they don’t have any signs of BHD.

In our research group, we are now investigating how this specific folliculin variant affects the expression of genes in key signaling pathways.

We know that Folliculin is important for the development and maintenance of the inner balance of the cells. When we searched for the scientific literature, we found out that there were animal models lacking two copies of FLCN and they have problems with development and growth as well as the immune system which are similar to what we observe in our patient. In our project, we study cells from our patient and compare them with cells from individuals that have two healthy copies of FLCN. We use different methods to understand how different genes and proteins inside the patient cells behave in the presence of two affected copies of FLCN when compared to healthy controls.

We hope that by studying the patient cells, we can learn more about how the FLCN gene works and how it causes a new syndrome that shows different signs compared to BHDS. Our research may also help us understand more about BHDS.