Identifying the genetic causes of Behçet’s Disease

Dr. Niamh Morgan is a postdoctoral researcher in Prof. Gerry Wilson’s research group in the UCD Centre of Arthritis Research. Niamh is working on a NCRC funded project that aims to understand the genetic causes of the rare auto-inflammatory disease; Behçet’s Disease .

Auto-inflammatory conditions are caused by the body eliciting an immune response in the absence of an infection. Niamh explains “All plants and animals have an innate immune system which acts as a rapid defence mechanism. This system is the first responder to threats, such as infections caused by pathogens or ‘germs’ like viruses and bacteria. In response to a pathogen, inflammatory signals are released in the infected area which prepares the body to fight the infection. People who have auto-inflammatory conditions commonly experience episodes of unprovoked inflammation that can affect one or multiple organs in the body”

In patients with Behçet’s Disease, this response leads to inflammation throughout the body. “Behçet’s Disease is an auto-inflammatory condition where patients’ symptoms include ulcers in the mouth or genitals, inflammation in the eye, rashes and, less commonly, inflammation of the bowels, large blood vessels and the brain”.

A Behçet’s Disease (BD)-like illness, affecting both adults and children, has been found in several unrelated families in different parts of the world, including Ireland. “In Ireland we have identified a number of familial and sporadic (a person has the disease, but members of their family do not) cases of a childhood BD-like disease”

While extremely rare, the incidence of a BD-like illness appears to be higher in Ireland than the global average. “Globally, it is estimated that less than 1 in 1000000 people are living with this condition. However, in Ireland this condition is becoming increasingly common. We are studying over 20 people affected with this condition, and we now know that there are more families with this condition that have not been included in our study. We can estimate approximately 1:200,000 people in Ireland”.

Auto-inflammatory conditions like Behçet’s Disease are believed to be caused by genetic changes. “It is thought to be caused by a combination of a large number of changes in the DNA, each contributing small but accumulative effects, and unknown environmental exposure(s)”.

In her NCRC funded research, Niamh is attempting to identify the genetic changes associated with cases of BD-like illness in Ireland. “We are using a genetics-based approach to identify DNA changes in patients that lead to this childhood BD-like disease. DNA is found in every cell in our body and is made up of over 19,000 genes. Within these genes, we each have about 24,000 changes to our DNA, but most of these changes do not cause disease. A doctor takes blood from the patient with childhood BD-like disease and sends it to our laboratory where we isolate the DNA from their blood cells. We then analyse the DNA to identify changes/mutations and use computational approaches to find out which of these changes are likely to cause the disease. Next, we use laboratory-based approaches, some of which study the blood cells of affected and unaffected family members, to understand how the identified mutations can disrupt the normal processes that the genes are involved in, and therefore lead to disease”.

Through this analysis, Niamh’s team have identified the genetic change in a family with Behçet’s Disease. “To date we have found a mutation in the first family, a large three generation family with four affected individual that is causing this disease. Over 19,000 genes in their DNA were analysed and it was found that all affected family members had the same mutation in one of the important genes that controls inflammation. This had to be validated in the laboratory by investigating how this mutation affects the normal function of the gene. In the lab, we have proved that this mutation prevents the gene from functioning properly and as a result, patients experience frequent episodes of inflammation and ulcers. We have also tested the affected members of the other families for the same mutation, but they do not have it. Furthermore, they don’t have any mutations in this gene at all. We believe that they have mutations in other genes that are important in the inflammatory process. We are currently analysing the DNA from the affected members of the other families, as well as the sporadic cases to find the disease-causing mutations”.

By understanding the genetic factors contributing to the BD-like illness, Niamh hopes her research will help clinicians identify the most appropriate and effective treatment strategies for these patients “The expected outcome of our research is to identify the genetic basis of this childhood BD-like disease in Irish families and individual cases. Our research will focus on uncovering evidence that allows doctors to choose the most appropriate treatment for each patient. How well a patient responds to treatment can be dependent on what genetic mutation is causing the disease. It is expected that the findings from this study will lead to earlier and better disease management, consequently preventing bodily damage and improving the quality of life for the affected children”.

Throughout her career, Niamh’s research has been focussed on understanding the root causes of rare diseases. “Carrying out research gives me a great feeling of accomplishment and that I am achieving significant goals. I was first introduced to the study of rare disease during a series of lectures in the final year of my Bachelor of Science degree at UCD. I learned that although a rare disease is rare, rare diseases are common, with more than 300 million people in the world living with a rare disease! Interestingly, unlike more complex and common disorders such as Type 2 Diabetes or Cancer that are caused by multiple factors, rare diseases are often caused by changes in a single gene. Unlike common diseases, however, there is very little research studying the cause of rare diseases as the output of the research may only benefit a small number of people, but I felt that it is important. The study of rare diseases sparked a passion in me and influenced my decision to pursue a PhD in UCD, researching the cause of a rare skeletal disease called Smith-McCort Dysplasia. Although my PhD research has contributed to that area of biology and disease, it struck me that nobody in Ireland has the condition that I studied. I wanted to make an impact closer to home. This is when I heard about the opportunity to work on the NCRC funded project awarded to Prof. Gerry Wilson in the UCD Centre for Arthritis Research, researching the genetic cause of an auto-inflammatory disease found in Irish patients. I believe that this research will positively contribute to the area of rare disease in Ireland and will directly influence the lives of patients living with this condition”.

Information on all UCD Centre for Arthritis Research studies are available at