Gerry Wilson

Down syndrome is a chromosomal disorder caused by full Trisomy 21 (95%), Robertsonian Translocation or Mosaicism. Approximately 110 babies with Down syndrome are born in Ireland each year, making Ireland’s birth rate of children with Down syndrome the highest in Europe. This puts Irish researchers in a unique position to engage in robust research into conditions that affect children with Down syndrome. A variety of medical conditions and immunological abnormalities are associated with Down syndrome. Immune dysregulation predisposes children with Down syndrome to high frequencies of haematologic malignancies, increased susceptibility to infections, and, most remarkably, a high incidence of autoimmune diseases, including arthritis. DA is an inflammatory joint condition affecting children with Down syndrome. The NCPR at OLCHC provides care to 40 children with DA, the largest reported cohort worldwide. Our research has demonstrated that the prevalence of DA is 18-21 times greater than Juvenile Idiopathic Arthritis (JIA) (JIA prevalence 1/1000).

Does genetic correlation mean disease causation? Arthritis is the single biggest cause of disability in Ireland. We carry out studies comparing the frequency of genetic variations in people with rheumatic disease versus healthy individuals. Results showed that a number of these genetic variations were present more often in individuals with disease, suggesting they may be associated with increased risk of developing the disease. Often, novel (new or previously unknown) variants are overlooked due to a lack of information or inability to use standard techniques to study them. My research focuses on studying these novel genes and variants to determine if there is a biological rationale for causation of disease rather than mere correlation with disease. The novel gene I’m currently investigating is called C5orf30. A variant within C5orf30 is associated with both risk and severity of rheumatoid arthritis (RA). To date, our research has demonstrated that C5orf30 does indeed have a causative role and is a previously unknown regulator of both tissue damage in RA and resolution of inflammation by immune cells.

How do people experience the burden of self-managing a chronic illness? It is a burden that is largely invisible and often difficult to express to family, friends and health care professionals. My project involves working with patients of rheumatoid arthritis to capture their “lived experience” and facilitate a better understanding of everyday life with a chronic illness. It will rely on participation and collaboration between the researcher and the researched. Ultimately, this work intends to improve society’s understanding of what it is like for people to self-manage rheumatoid arthritis and devise ways to best support them.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory disease of childhood which affects ten child per million. Auto-inflammatory diseases lead to recurrent episodes of inflammation in specific parts of the body with no obvious trigger. This study will look at a large Irish CRMO population using state-of-the-art technology to study patients’ genes. Genes are made of parts called introns and exons. Exons are the part of the gene that make proteins. Proteins tell a cell what type of cell it is and how it should behave. All the exons together are called the exome. The specific genetic test we propose to do is called whole exome sequencing and looks at the whole exome. Scientists compare the sequence of a patient’s exome with that of a normal exome. The location of differences in the sequence are marked. If the difference affects genes that control bone growth, inflammation and the immune system it will be studied further because it may cause CRMO.

Rheumatoid Arthritis (RA) varies from a mild to a severe, unremitting illness characterized by uncontrolled inflammation with consequent damage to cartilage and bone of joints. It is now known that our DNA determines the likelihood of severity of disease. The study of patients DNA can then facilitate personalized approach where patients likely to develop severe disease will receive more aggressive treatment compared to the patients with mild disease. My project will identify genetic variants associated with severity of RA which will help us to establish a risk prediction score for early identification and stratification of patients. The results obtained during this study will also assist the clinicians in determining the optimal treatment to be given to patients, more quickly and efficiently.