| Dr Daire O'Leary | UCD Newman Fellow, UCD CAR |
This project is funded by the National Children's Research Centre.
CNO: A Rare Disease of Children and Teenagers, a video we made for Rare Disease Day 2018
Chronic nonbacterial osteomyelitis (CNO) is a serious, rare auto-inflammatory disease. The cause of CNO is not known. Some patients’ CNO is worse than others’. We want to know why. We will use state-of-the-art technology to look at patients’ genes. We will see if there’s an association between certain genes, certain bone biopsy findings and how bad the CNO is. This might help us figure out why CNO happens. Then we might be able to treat it more effectively. We think that slight differences in genes might help explain why CNO happens because some patients with CNO have a brother or sister or parent with CNO.
In CNO, bones get inflamed without a good reason. This can make them painful, swollen and hard to use. Some patients don’t have swelling that we can see which makes it hard to diagnose. Patients have scans done to help us to diagnose CNO. We often need to take a sample or biopsy of the bone to make sure it is not cancer or infection. CNO is treated by paediatric rheumatologists. If we don’t treat CNO, it can lead to poor growth or fracture.
Chronic nonbacterial osteomyelitis (CNO) is a rare auto-inflammatory disease of childhood which affects one child per million. Auto-inflammatory diseases lead to recurrent episodes of inflammation in specific parts of the body with no obvious trigger. In CNO, this inflammation occurs in bone leading to localised pain, swelling and difficulty using the affected parts of the body. Poor growth or fractures in the affected bone leads to unequal limb length or abnormal curvature of the spine (scoliosis) which are serious long-term problems. CNO affects one or many bones and symptoms usually recur over many years. The diagnosis is based on the patient’s symptoms and scans of the affected bones although a biopsy sample of the bone is often needed to exclude other causes of bone pain such as infection or cancer.
The cause of CNO is not known but it is likely that there is a genetic basis because it sometimes affects more than one member of a family. In addition, about 50% of patients with CNO have a first or second degree relative with another chronic inflammatory condition such as psoriasis, arthritis or inflammatory bowel disease. Studies have looked at a small number of genes which are known to cause other auto-inflammatory diseases but have failed to find a gene which causes CNO. Since 2006, 43 patients have been diagnosed with CNO at the National Centre for Paediatric Rheumatology (NCPR) in Dublin. This indicates that the disease affects around 1 in 100,000 rather than 1 in a million. This may mean that there is a stronger genetic cause in the Irish population.
This study will look at a large Irish CNO 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 CNO.
The outcome will be the identification of differences or variants in one or more genes that could cause CNO. This information may allow us to personalise treatment to suit individual patients and control the disease more effectively. This will improve the quality of life of patients with CNO with less disturbance to schooling, physical activities and social interactions. It will also reduce healthcare costs associated with hospital admissions. The information will lead to further studies which will look at the function of the cells that the genes control.
The work will be completed by Dr Daire O'Leary and is supervised by Professor Gerry Wilson (UCD), Dr Orla Killeen (Our Lady's Children's Hospital Crumlin) and Professor Michael McDermott (University of Leeds).