dc.contributor.author | Farrar, Gwyneth | |
dc.date.accessioned | 2022-03-07T15:35:26Z | |
dc.date.available | 2022-03-07T15:35:26Z | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022 | en |
dc.identifier.citation | Stephenson, K.A.J. and Zhu, J. and Dockery, A. and Whelan, L. and Burke, T. and Turner, J. and Oâ byrne, J.J. and Jane Farrar, G. and Keegan, D.J., Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing, International Journal of Molecular Sciences, 2022, 23, 2 | en |
dc.identifier.other | Y | |
dc.identifier.uri | http://hdl.handle.net/2262/98251 | |
dc.description.abstract | Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner. | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | International Journal of Molecular Sciences; | |
dc.relation.ispartofseries | 23; | |
dc.relation.ispartofseries | 2; | |
dc.rights | Y | en |
dc.subject | inherited retinal degenerations (IRDs) | en |
dc.subject | panel-based next-generation sequencing (pNGS) | en |
dc.subject | autosomal recessive disease | en |
dc.subject | Whole exome sequencing | en |
dc.subject | Unresolved inherited retinal degenerations | en |
dc.subject | Single gene sequencing | en |
dc.subject | Retinal dystrophy | en |
dc.subject | Next generation sequencing | en |
dc.subject | Genetic testing | en |
dc.subject | Inherited retinal degenerations | en |
dc.title | Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/gjfarrar | |
dc.identifier.rssinternalid | 239065 | |
dc.identifier.doi | http://dx.doi.org/10.3390/ijms23020995 | |
dc.rights.ecaccessrights | openAccess | |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.contributor.sponsorGrantNumber | 16/1A/4452 | en |