Abstracts

Rationale: In the epilepsy clinic, genetic diagnostic testing is primarily conducted in the paediatric arena, while the utility of such testing is less well understood in adult patients. Here, we investigated the yield of genomic testing in a group of adult patients and compared the yield directly to a parallel paediatric cohort. Methods: Patient trios (proband and both parents) were recruited through a network of paediatric and adult tertiary referral centres. Whole exome sequencing was conducted using NimbleGen SeqCap EZ library preparation and llumina 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 (MDT).  Results: To date, 83 trios have been recruited. 77 trios (61 adult, 16 paediatric) have been exome sequenced and discussed at MDT.  A molecular diagnosis (ACMG defined “pathogenic”/ “likely pathogenic variant”) was obtained in 17/77 (22%) patients. The rate of molecular diagnosis was higher in the paediatric group (31%) than the adult group (20%). Conclusions: Although the rate of diagnosis was higher in the paediatric cohort, we successfully identified a molecular diagnosis in 20% of adult epilepsy patients. Our findings indicate that exome testing has similar utility in both adult and paediatric cohorts and should be considered for diagnostic testing in both epilepsy patient groups. Funding: Funding received from eHealth Ireland.