Identification of the genetic causes of developmental delay with mitochondrial dysfunction in the Irish Traveller Population

Lead Researcher:

Dr Sally Ann Lynch

Award Date:

1 January 2013

Host Institution:

Children’s Fund for Health

Scheme:

Medical Research Charities Group Co-Fund Award

Summary:

The metabolic service in Temple Street Children's University Hospital is asked to investigate many children who present with developmental delay/intellectual disability. The causes of developmental delay are numerous and baseline investigations can uncover the cause in ~50-70%. However, for many families with a rare form of developmental delay, standard routine investigations do not provide a diagnosis, resulting in significant frustration for the families and clinicians. In many cases, we know that the cause of their child's disorder is genetic but we cannot pinpoint the gene involved. Their child undergoes numerous testssome painful- and yet no cause is identified. In such cases, it is unclear whether this could happen again should the family have more children. Sometimes, this can lead to loss of trust in the physicians.
Most genes that cause rare disorders have not yet been found, mainly because gene discovery studies are difficult to perform when DNA from only a small number of affected children is available. Recently a new technology, called Next-Generation Sequencing, has been developed which allows an individual's entire genetic code (~22,000 genes) to be analysed in a single experiment. This technology has revolutionised the study of rare genetic disorders because it is now possible to find disease-causing genes using a relatively small number of patients. Our own research confirms this; we successfully identified several new disease genes in Irish families, five of which were isolated by analysing the DNA of an individual patient.
We propose a study where we will offer families Next-Generation research to try and find the gene causing their child's developmental delay and associated problems. Our aim is to identify disease genes so that these families can be offered accurate genetic counselling. We will also develop simple genetic blood tests that can be used for diagnostic and carrier testing. The tests will allow earlier diagnosis for future children (as yet unborn) as we expand our knowledge of the disease genes that cause developmental delay in the Irish population.
The new genetic tests will improve care of patients in the future as it will allow us make diagnoses earlier thereby reducing the number of invasive tests required before confirmation of diagnosis. Disease gene identification means that we can offer immediate advice on recurrence and prevention to the family. It also provides a better understanding of disease and allows us to explore possible treatments.