Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations
| Autor: | Hilary Dempsey, Paul F. Kenna, Karen Collins, James J. O’Byrne, Laura Whelan, Emma Duignan, Jacqueline Turner, Julia Zhu, Adrian Dockery, Laura Brady, Giuliana Silvestri, Shana Routledge, Rebecca Cairns, Conor Patrick Malone, David J Keegan, Rajiv Pandey, Niamh Wynne, Elaine Crossan, G. Jane Farrar, Kirk Stephenson |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Public and patient involvement Psychological intervention Clinical diagnostic algorithm Disease Bioinformatics Inherited retinal degenerations 03 medical and health sciences 0302 clinical medicine Retinal Dystrophies Genotype Humans Medicine Exome Pharmacology (medical) Letter to the Editor Genotyping Genetics (clinical) Whole genome sequencing business.industry Ocular genetics Retinal Degeneration Retinal dystrophy General Medicine Human genetics Pedigree Clinical trial 030104 developmental biology Genetic diagnosis Mutation 030221 ophthalmology & optometry business Ireland |
| Zdroj: | Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-8 (2021) Orphanet Journal of Rare Diseases |
| ISSN: | 1750-1172 |
| Popis: | Introduction Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, manifesting variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interventions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective pathway for assessment and management is required. Methods Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service (Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis, functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors) reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing interventions, and novel therapies/clinical trials. Results and discussion Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/support services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000 allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding has transferred from charitable sources to government resources. Conclusion Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model could be used to develop similar IRD programmes in small/medium-sized nations. |
| Databáze: | OpenAIRE |
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