Abstracts

Rationale: PISCES (Providing Individualised Services and Care in Epilepsy) is a nationwide programme of innovation in Ireland to create conditions for eHealth enabled proactive, precision and personalised (PPP) medicine which can lead to optimised diagnostics, deliver targeted therapy, improve patient participation, achieve better health outcomes and realize best value from finite healthcare resources for people with epilepsy. As part of the PISCES project, we are conducting trio genomic testing in 50 adults and 50 children with severe forms of epilepsy of unknown cause, and integrating results of this testing into the clinical care pathway and a bespoke epilepsy electronic patient record using enabling eHealth technologies.  This work describes 1) the Lighthouse Project exome sequencing and array comparative genomic hybridization (CGH) process and 2) the results of genomic testing to date. Methods: Patients are recruited through a national network of paediatric and adult tertiary referral centres. Whole exome sequencing was conducted using NimbleGen SeqCap EZ library preparation and an Illumina NextSeq sequencer, via a research pipeline. In parallel, copy number analysis was performed using Agilent SureTag/Agilent Human Genome CGH Microarray kit. A custom, in-house bioinformatics pipeline was used for the analysis of the resulting sequencing data. Identified variants were stratified according to pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) guidelines and discussed at a multi-disciplinary team meeting.  Clinical and genomic data is entered into a bespoke clinical epilepsy electronic patient record, with a novel genomics module.  Results: At the time of submission, 41 trios have been recruited and 32 trios have completed genomic testing. Pathogenic/likely pathogenic variants have been identified in a number of these trios and these variants are undergoing confirmatory testing via an accredited service provider. Mutations in eight known "epilepsy genes" have been identified thus far, including GRIN2A, SCN9A, CHD2, DCX, ALDH5A1, and OPHN1. Conclusions: This project allows to identify barriers and facilitators to the integration of genomics into the clinic and the electronic patient record, using epilepsy as a model of a chronic, neurological disease. Whole exome sequencing and array CGH have been used to successfully identify candidate ACMG-defined pathogenic variants which will be integrated into the clinical care pathway using the PISCES eHealth technologies. Funding: PISCES is one of three Lighthouse Projects funded by eHealth Ireland and the Health Services Executive (HSE) to help build an understanding of the benefits of eHealth technologies in the Irish Healthcare System