Academic Centre on Rare Diseases

Centre Overview

The UCD Academic Centre on Rare Diseases (ACoRD) was awarded formal centre status in June 2013. The focus of the centre is to investigate rare genetic diseases, particularly those affecting the Irish population and the Irish Traveller population.

The Centre’s aims are focused on the study of rare genetic diseases, with a view to the identification of the mutation(s) causing the disease. Once a causal mutation(s) is established, the objective is to develop diagnostic tests for translation back into a clinical setting. Once a gene is implicated, our PIs work to further investigate the gene function and biological pathways involved in the condition. The ultimate aim is to investigate those conditions / genes which might be amenable to drug targeting or gene therapy.

Rarely in a lifetime does a scientific or medical field of research ‘come of age’. The revolution that was the ‘Human Genome Project’, coupled with the latest technological advances in genomics is set to transform the field of rare genetic diseases. An ad hoc group of UCD based clinicians, scientists, specialists in bioinformatics and cell biologists have long since recognised these developments, and the rare disease group – prior to its establishment as a centre – has achieved considerable national and international recognition.

More Information About UCD Academic Centre on Rare Diseases

Rather than employing the traditional approach of a large, disease-specific research group which focuses on a common disorder, our PIs focus on rare genetic disorders and utilise new tools from the genomics revolution to aid our study of common and rare disorders. We pursue an integrated approach to our work, which involves close collaboration across clinical and research teams.

In Ireland there are about 280,000 individuals with a rare disease. In addition, there are approximately 60 identified recessive disorders in the Traveller population. In a pilot study we have completed data analysis on six of ten rare disorders of unknown genetic basis, affecting 25 small Irish families. Of the six studies, the disease mutation has been successfully identified for five families, of which three studies have been published to date, with four translated back into the clinical setting. This translational success demonstrates our ability to identify rare disease genes in small families.

We have recently consolidated our various working groups under one recognisable centre to harness the successful outputs and future studies for UCD. Ireland is required to submit a National Plan for Rare Diseases by 2013. A UCD academic centre on rare diseases is uniquely positioned to contribute to this plan. The centre aims to make a meaningful contribution in the progression of gene discovery to diagnostics, and ultimately in the cure or prevention of serious genetic conditions.

Research at UCD Academic Centre on Rare Diseases is currently addressing a multiple of rare genetic conditions including:

  • Autism
  • ACTH/NK cell deficiency
  • Infantile liver failure
  • Anophthalmia
  • Dilated Cardiomyopathy
  • Micocephaly
  • Primary Ciliary Dyskinesia
  • Episodic Ataxia
  • Immunodysplasia
  • Landau-kleffner Syndrome LKS
  • Ptosis +
  • FAS
  • Autism & Methylation
  • Epilepsy and Regression
  • Multiple ataxia families (5 additional families consented, more being approached)
  • A large Irish family with paryoxysmal dyskinesia
  • A family with developmental delay and iron absorption dysfunction
  • A family with calcification of the brain in 2 children
  • 2 Samples with sex reversal
  • Sample with cutus gyratus
  • 2 sibs with profound growth retardation
  • Hypothalamic hamartomas (HH)
  • Rare skin condition
  • Subglottic stenosis
  • Dandy walker syndrome
  • Kartageners syndrome (mapped to novel locus on X-chromosome)
  • Pyloric/ Intestinal Web
  • Epileptic encephalopathy family
  • VUR

Research Team

Dr Sean Ennis
Lecturer in Medical Genetics

Professor David Barton
Associate Professor

Dr Oliver Blacque
College Lecturer

Dr Paula Byrne
Senior Lecturer in Medical Genetics

Dr Ellen Crushell
Consultant Paediatrician

Dr Patrick Felle
Senior Lecturer/Associate Dean

Prof Andrew Green
Professor of Medical Genetics

Professor Michael Hutchinson
Consultant Neurologist

Dr Breandán Kennedy
Senior Lecturer/Conway Fellow

Prof Mary King
Professor of Paediatrics/Head of Subject

Dr Sally Ann Lynch
Consultant Geneticist/Senior Clinical Lecturer

Professor Eileen Treacy
Consultant in Inherited Metabolic Disorders

Associated Researchers

Dr Jillian Casey                                                 
National Children's Research Centre

Dr Judith Conroy                                             
Temple Street Children’s University Hospital

Dr Harinder Gill                                
National Centre for Medical Genetics     

Dr Tiago R Magalhaes                                    
National Children's Research Centre

Dr Paul McGettigan                                        
UCD, School of Agriculture & Food Science

Dr Regina Regan                                              
National Children's Research Centre

Health Context

In Ireland there are upwards of about 280,000 individuals with a rare disease and approximately 60 recessive disorders within the Irish Traveller population. Worldwide there is an estimated 350 million people affected with a rare disease at any given time. Currently there are over 7,000 recognised rare diseases. Within the European Union a rare disease is one that affects less than one in every 2,000 individuals.

Because of the number of individuals afflicted by any one rare disease is so small resources to investigate the causes of rare diseases, to develop diagnostic testing and to cure or prevent serious genetic conditions has tended to be very limited.

The Academic Centre on Rare Diseases brings together resources and the inter-disciplinary expertise of scientists with a focus on finding the genetic cause of rare diseases and translating these findings back to a clinical setting. 

This involves many inter-disciplinary research links between clinical geneticists, non-clinical geneticists, bioinformaticians, computer scientist, cell biologists, molecular diagnostic clinical scientists and pharmacologists.

Director Interview

In conversation with Claire O'Connell

There are some things that run in families, like red hair and blue eyes. And sometimes medical conditions do to. When that happens, it can be helpful to know what genes are involved, to inform genetic counselling, to develop tests to help diagnosis and possibly even to identify new molecular targets for treatments. Dr Sean Ennis is using genetic techniques to analyse a range of inherited conditions, from relatively common disorders such as autism, to rare diseases that tend to concentrate in families.

New technologies, quicker results

The technology to analyse human genetics has developed rapidly over the last two decades or so, explains Dr Ennis, who is a Lecturer at UCD School of Medicine & Medical Science and a Principal Investigator at the National Centre for Genetics in Crumlin.

There was a time when if you wanted to work out the mutations, or changes in DNA, that were linked to an inherited disease, you would get samples from the patients, analyse them and then put them in the freezer and wait for the next generation to be born so you could continue the study,” he says.

Times have moved on, he notes, and now approaches such as exome sequencing, which works out the ‘letters’ in DNA that encode genes, and other techniques offer the chance to find important mutations more rapidly.

Autism - genetic complexity

For many years, Dr Ennis has been working on the genetics of autism with colleagues in TCD, Ireland and internationally. One of their major breakthroughs was to highlight the complex nature of mutations in the condition - by genotyping 9,000 individuals in 3,000 families and looking to see whether there were common changes in the DNA letters that were linked with autism. The results were surprising, and they changed the thinking about autism genetics, explains Dr Ennis.

 Prior to that study it was thought there were a few common genes involved in autism,” he says. “But our data showed that there wasn’t, that instead there were multiple rare variants.”

Rare diseases - the genetic link

While Dr Ennis remains involved in autism research, he and colleagues at UCD have also developed a particular strength in investigating the genetics of inherited rare diseases. By their nature, individual cases rare diseases may not be numerous, but the sheer numbers in the rare disease category quickly add up, and most have a strong genetic component, he explains. “There are about 6,000 to 8,000 known rare diseases, and about 80 per cent of them are genetic in background.”

Because many of those rare diseases tend to involve a small number of key genes and are concentrated in families, it can make the hunt for participating genes and mutations more directed, explains Dr Ennis.

And at UCD there is considerable interest in finding out more about inherited rare diseases among the Traveller community in Ireland, he adds. “We reckon there are around 60 genetic conditions associated with the Traveller community here, and we are looking at some of these conditions.”

An eye to diagnosis

They have already had considerable success. One breakthrough was in a rare disease called micro-anophthalmia, where children are born with eyes that are small or missing. One family had seven affected members, so the researchers, including Dr Jillian Casey, compared at genetic information from affected people and their close relatives and homed in on a relatively small stretch of DNA that contained two genes of interest.

One of those genes was STRA6, which in involved in vitamin A uptake, an important factor in eye development, and the UCD/Crumlin study showed that mutated STRA6 was at the root of micro-anophthalmia. The findings led to the development of a service test that can be used to inform genetic counselling for potentially affected families.

That’s just one of several examples where, by focusing on a rare disease in related groups, UCD research has unveiled important genetic information about rare conditions, and Dr Ennis points out that knowing about these key molecular events can lead to better diagnostic tests and, in the longer term, could possibly inform new approaches to treatment.

Rare Diseases Centre

He now wants to consolidate the ongoing work in rare diseases through a proposed new Rare Diseases Centre, which would harness the expertise that has grown organically in UCD, Crumlin and the Children’s University Hospital at Temple Street in recent years.  

My aim in terms of rare diseases is to take it beyond individual investigators,” he says.

The study of rare diseases is bringing together clinicians, geneticists, experts in animal models and others who are in position to translate findings into to the clinic. We want to get the research in a more established framework so we can look for longer-term funding and build strategies around rare diseases.

Editors note: the Centre gained formal status in Summer 2013.

Donations

  • It is possible to make a donation towards ‘Research into Rare Diseases’.
  • This may be made through the UCD Foundation web page by selecting ‘Medical Research – Rare Diseases’ from the dropdown menu.

Philanthropic or corporate donations may be made by contacting:

Jessica Kavanagh
Director
Trusts & Foundations
UCD Foundation
E: jessica.kavanagh@ucdfoundation.ie
T: + 353 1 716 1268
W: UCD Foundation (donations)