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 based at MMUH includes Ms Jackie Turner as Genetic Counsellor and Dr James O’Byrne, the clinical geneticist.
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 aims 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.
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
Target 5000 outputs
The publications listed below are outputs generated from the Target 5000 funding provided by Fighting Blindness. In some instances, the research in these publications was also part-funded by other sources.
2023:
- Stephenson KAJ, Whelan L, Zhu J, Dockery A, Wynne NC, Cairns RM, Kirk C, Turner J, Duignan ES, O’Byrne JJ, Silvestri G, Kenna PF, Farrar GJ, Keegan DJ. Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review. Invest Ophthalmol Vis Sci. 2023 Jul 3;64(10):23. doi: 10.1167/iovs.64.10.23. PMID: 37466950; PMCID: PMC10362925.
- Whelan, L., Dockery, A., Stephenson, K.A.J. et al. Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients. Sci Rep 13, 9380 (2023). https://doi.org/10.1038/s41598-023-35889-9
- Quigley C, Hanrahan G, Stephenson K, Ahmed S, Mukhtar M, Cassidy L. Cardiac conduction abnormalities in Leber Hereditary Optic Neuropathy and asymptomatic maternal relatives. Eye (Lond). 2023 Mar 6. doi: 10.1038/s41433-023-02466-3. Epub ahead of print. PMID: 36879160.
- Quigley C, Stephenson KAJ, Kenna P, Cassidy L. Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups. Int J Mol Sci. 2023 Jan 5;24(2):1068. doi: 10.3390/ijms24021068. PMID: 36674591; PMCID: PMC9864201.
2022:
- O’Connell A, Zhu J, Stephenson KAJ, Whelan L, Dockery A, Turner J, O’Byrne JJ, Farrar GJ, Keegan D. MFRP-Associated Retinopathy and Nanophthalmos in Two Irish Probands: A Case Report. Case Rep Ophthalmol. 2022 Dec 16;13(3):1015-1023. doi: 10.1159/000527260. PMID: 36605040; PMCID: PMC9808125.
- de Bruijn SE, Rodenburg K, Corominas J, Ben-Yosef T, Reurink J, Kremer H, Whelan L, Plomp AS, Berger W, Farrar GJ, Ferenc Kovács Á, Fajardy I, Hitti-Malin RJ, Weisschuh N, Weener ME, Sharon D, Pennings RJE, Haer-Wigman L, Hoyng CB, Nelen MR, Vissers LELM, van den Born LI, Gilissen C, Cremers FPM, Hoischen A, Neveling K, Roosing S. Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease-associated genes. Genet Med. 2023 Mar;25(3):100345. doi: 10.1016/j.gim.2022.11.013. Epub 2022 Dec 16. PMID: 36524988.
- Zhu J, Stephenson KAJ, Dockery A, Turner J, O’Byrne JJ, Fitzsimon S, Farrar GJ, Flitcroft DI, Keegan DJ. Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population. Genes (Basel). 2022 Mar 29;13(4):615. doi: 10.3390/genes13040615. PMID: 35456422; PMCID: PMC9033125.
- Stephenson KAJ, McAndrew J, Kenna PF, Cassidy L. The Natural History of Leber’s Hereditary Optic Neuropathy in an Irish Population and Assessment for Prognostic Biomarkers. Neuroophthalmology. 2022 Mar 2;46(3):159-170. doi: 10.1080/01658107.2022.2032761. PMID: 35574161; PMCID: PMC9103396.
- O’Connell A, Stephenson KAJ, Zhu J, FitzSimon S. Coats-like exudative vitreoretinopathy (CLEVER) in CEP290 inherited retinal degeneration. BMJ Case Rep. 2022 Feb 15;15(2):e247229. doi: 10.1136/bcr-2021-247229. PMID: 35168937; PMCID: PMC8852659.
- Velde HM, Reurink J, Held S, Li CHZ, Yzer S, Oostrik J, Weeda J, Haer-Wigman L, Yntema HG, Roosing S, Pauleikhoff L, Lange C, Whelan L, Dockery A, Zhu J, Keegan DJ, Farrar GJ, Kremer H, Lanting CP, Damme M, Pennings RJE. Usher syndrome type IV: clinically and molecularly confirmed by novel ARSG variants. Hum Genet. 2022 Feb 28. doi: 10.1007/s00439-022-02441-0. Epub ahead of print. PMID: 35226187.
- Stephenson KAJ, Zhu J, Dockery A, Whelan L, Burke T, Turner J, O’Byrne JJ, Farrar GJ, Keegan DJ. Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing. Int J Mol Sci. 2022 Jan 17;23(2):995. doi: 10.3390/ijms23020995. PMID: 35055178; PMCID: PMC8780304.
- Stephenson KAJ, Zhu J, Dockery A, Whelan L, Burke T, Turner J, O’Byrne JJ, Farrar GJ, Keegan DJ. Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing. Int J Mol Sci. 2022 Jan 17;23(2):995. doi: 10.3390/ijms23020995. PMID: 35055178; PMCID: PMC8780304.
2021:
- Green Sanderson K, Stephenson KAJ, Dockery A, Keegan DJ. Pigmentary retinopathy masked by asymmetric acquired phenomena. BMJ Case Rep. 2021 Nov 1;14(11):e246982. doi: 10.1136/bcr-2021-246982. PMID: 34725069; PMCID: PMC8562530.
- Reurink J, Dockery A, Oziębło D, Farrar GJ, Ołdak M, Ten Brink JB, Bergen AA, Rinne T, Yntema HG, Pennings RJE, van den Born LI, Aben M, Oostrik J, Venselaar H, Plomp AS, Khan MI, van Wijk E, Cremers FPM, Roosing S, Kremer H. Molecular Inversion Probe-Based Sequencing of USH2A Exons and Splice Sites as a Cost-Effective Screening Tool in USH2 and arRP Cases. Int J Mol Sci. 2021 Jun 15;22(12):6419. doi: 10.3390/ijms22126419. PMID: 34203967; PMCID: PMC8232728.
- Dockery A, Whelan L, Humphries P, Farrar GJ. Next-Generation Sequencing Applications for Inherited Retinal Diseases. Int J Mol Sci. 2021;22(11):5684. Published 2021 May 26. doi:10.3390/ijms22115684.
- 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
2020:
- 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 KA, O’Keefe M, Keegan DJ. Surgical management of non-syndromic ectopia lentis. Int J Ophthalmol. 2020;13(7):1156-1160. Published 2020 Jul 18. doi:10.18240/ijo.2020.07.21
- 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
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