| Working Group 6 | |
| WG Name | Next-generation genomics and platforms |
| WG Leads | Brent Fogel (Los Angeles, USA) Andrea Nemeth (Oxford, UK) Matthis Synofzik (Tübingen, Germany) Stephan Zuchner (Miami, USA) |
| The goal of this working group is to identify and enrich genetically stratified ataxia patients for trial-readiness natural history studies and treatment trials. This will be achieved by establishing a genetic ataxia diagnosis for as many ataxia patients as possible, in particular for genetically still undefined and “hard-to-diagnose” ataxia patients, and by prioritizing genetic ataxia conditions which are already druggable (e.g. COQ8A ataxia, Niemann Pick Type C ataxia; ataxia patients with splice mutations amenable for n-of-1 ASO treatments) or are currently being prepared for trial-readiness/druggability (e.g. ion channel SCAs, ARSACS, SPG7, etc.).
This will be achieved by work on three parallel project Aims. For ataxia patients still without a genetic ataxia diagnosis, Aim #1 will identify mutations in known ataxia genes by (i) increasing the percentage of unsolved ataxia patients receiving WES/WGS, i.e. generating novel WES/WGS datasets (goal #1); (ii) reanalyzing existing WES/WGS datasets of patients where no causative mutation has been found so far (goal #2); and (iii) clarifying the pathogenicity of VUS in SCA/ARCA genes in still unsolved patients (goal #3). Aim #2 will identify mutations in novel ataxia genes for these undiagnosed patients. It will be based on establishing optimal and novel systematic genomic strategies to identify novel ataxia genes (goal #4). The key to both Aims #1 and #2 will be large-scale cross-center sharing of existing ataxia NGS datasets using three readily mineable collaborative ataxia genomics platforms. Aim #3 will implement ways to incorporate newly genetically diagnosed ataxia patients into existing ataxia trial-readiness registries (SCA registry, ARCA registry, etc.) (goal #5), and to share newly identified potentially treatable genomic mechanisms with other working groups in the AGI (goal #6). |
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