The Target 5000 team brings together clinicians, scientists, ophthalmologists in training, a genetic counsellor, a clinical geneticist, imaging technicians, genealogists, research nurses and support staff.
There are three clinical sites as part of Target 5000, two in Dublin and one in Belfast. Prof David Keegan at the Mater Misericordiae University Hospital (MMUH) is the coordinating clinical lead and working closely with Dr Paul Kenna and Dr Emma Duignan at the Royal Victoria Eye and Ear Hospital, Dublin and Ms Giuliana Silvestri at Belfast Health and Social Care Trust in Northern Ireland.
The research arm is led by Prof Jane Farrar at Trinity College Dublin and includes research groups in Dublin and Radbound University, Nijmegen, the Netherlands.
The Clinical Genetics Team is based at MMUH and includes Ms Jackie Turner as Genetic Counsellor and Dr James O’Byrne, the clinical geneticist.
Target 5000 Clinical Fellows (ophthalmologists in training) are Dr Niamh Wynne at the Royal Victoria Eye and Ear Hospital Research Foundation and Dr Julia Zhu at Mater Misericordiae University Hospital in Dublin.
Genetic testing for an inherited retinal degeneration (IRD) is an important component of a diagnosis, allowing for a greater understanding of the condition and how it may affect other family members. Furthermore, recent advances in gene-specific therapies have made the issue of genetic diagnosis of IRD all the more pressing.
The dedicated and experienced team aim to genetically characterise the population of Ireland affected by inherited retinal degenerations. To date, over 900 DNA samples have undergone next generation sequencing (NGS), using a capture panel with 254 genes known to be associated with IRDs.
Many more samples have undergone alternative sequencing methods and reanalysis using updated software tools. Potential disease-causing mutations have been identified in approximately 65% of samples. Following the identification of a positive research grade result, these samples are then sent for confirmatory testing at a clinically accredited laboratory.
To address the remaining 35%, the team in collaboration with their colleagues in The Netherlands, continue to dig deep into the genetic data in the pursuit of identifying, as yet unknown, novel genetic mutations. The team have also dedicated significant efforts towards optimising the sequencing of regions within specific IRD genes as well as improving the coverage of the mitochondrial genome, with the goal of increasing the number of unresolved cases.
This project continues to contribute to the global knowledge of genetic information for inherited retinal degenerations. New phenotypes have been identified for known inherited retinal degeneration genes leading to a reassessment of original clinical diagnosis. The discovery arm of this research is exciting and may result in the identification of new genes not previously known to be associated with retinal disease.
Each presentation of our findings to local, national and international audiences has untold ripple effects in the scientific community – Target 5000 researcher
Recent publications from the Target 5000 team:
Zhu J, Stephenson KAJ, Farrar GJ, Turner J, O’Byrne JJ, Keegan D. Management of significant secondary genetic findings in an ophthalmic genetics clinic. Eye (Lond). 2021 May 3. doi: 10.1038/s41433-021-01557-3. Epub ahead of print. PMID: 33941876.
Stephenson KAJ, Zhu J, Wynne N, et al. Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations. Orphanet J Rare Dis. 2021;16(1):200. Published 2021 May 5. doi:10.1186/s13023-021-01841-1
Whelan L, Dockery A, Wynne N, et al. Findings from a Genotyping Study of Over 1000 People with Inherited Retinal Disorders in Ireland. Genes (Basel). 2020;11(1):105. Published 2020 Jan 16. doi:10.3390/genes11010105
Stephenson KAJ, Dockery A, O’Keefe M, Green A, Farrar GJ, Keegan DJ. A FBN1 variant manifesting as non-syndromic ectopia lentis with retinal detachment: clinical and genetic characteristics. Eye (Lond). 2020;34(4):690-694. doi:10.1038/s41433-019-0580-2
Application of next generation sequencing for the genetic characterisation of Irish retinal degeneration patients
Prof Jane Farrar, Trinity College Dublin
Characterising the IRD population in Northern Ireland through an an all-Ireland retinal degenerations partnership
Ms Giuliana Silvestri, Belfast Health and Social Care Trust, Northern Ireland
Shedding light on unexplained inherited retinal diseases in Ireland and the Netherlands
Prof Frans Cremers, Radbound University, the Netherlands and Prof Jane Farrar, Trinity College Dublin