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. 2025 Jun 22.
doi: 10.1111/cge.70008. Online ahead of print.

Diagnostic Utility of Exome Data Reanalysis After In Silico Multi-Gene Panels or Clinical Exome Testing for Patients With Epilepsy and Developmental Delay/Intellectual Disability: A Retrospective Cohort Study

Alexanne Cuillerier  1 , Andrea Goodman  1 , Chloe Lawrence  1 , Noémie Villeneuve-Cloutier  2 , Christine M Armour  2 , Priya T Bhola  2 , Danielle K Bourque  3 , Melissa T Carter  2 , Joanna Lazier  2 , Sarah L Sawyer  2 , Maha Saleh  4   5 , Chitra Prasad  4   5 , Victoria M Siu  4   5 ; Care4Rare Canada Consortium  1 ; Kym M Boycott  1   2 , Taila Hartley  1 , David A Dyment  1   2 , Tugce B Balci  4   5
Affiliations

Diagnostic Utility of Exome Data Reanalysis After In Silico Multi-Gene Panels or Clinical Exome Testing for Patients With Epilepsy and Developmental Delay/Intellectual Disability: A Retrospective Cohort Study

Alexanne Cuillerier et al. Clin Genet. .

Abstract

Epilepsy is a relatively common condition with genetic factors contributing significantly to its etiology. Advances in next-generation sequencing have dramatically increased the number of known epilepsy genes, improving diagnostic capabilities and patient care. However, 50%-80% of epilepsy patients remain undiagnosed after genomic testing, which includes chromosomal microarray, multigene panels, and genome-wide sequencing. Reanalysis of existing exome sequencing data has shown promise in increasing diagnostic yield. In this study, we reanalyzed exome sequencing data from 87 individuals with unsolved epilepsy and developmental delay or intellectual disability in Ontario, Canada. Our approach combined clinical and translational research methodologies to identify genetic variants linked to epilepsy. We obtained a diagnostic yield of 14.9%, solving 13 participants, with 11 involving known genes and two novel gene discoveries. In addition, 11 potential diagnoses were identified, suggesting that further investigation could confirm additional diagnoses. Factors such as the inclusion of additional family data, new disease-gene associations, and technological advancements contributed to these findings. This study highlights the importance of reanalysis as a cost-effective and timely approach to improving diagnostic yield in epilepsy associated with neurodevelopmental delay.

Keywords: diagnostic yield; epilepsy; exome re‐analysis; intellectual disability; next‐generation sequencing.

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