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Implementation of Epilepsy Multigene Panel Testing in Ontario, Canada

  • David A. Dyment (a1) (a2), Asuri N. Prasad (a3), Kym M. Boycott (a1) (a2), Grace U. Ediae (a2), Taila Hartley (a2), Ayman Hassan (a4), Katherine E. Muir (a5), Murray Potter (a6), Lysa Boisse Lomax (a7), Olga Jarinova (a1) (a2), Bekim Sadikovic (a8) (a9), Dimitri J. Stavropoulos (a10) and O. Carter Snead (a11)...

Abstract:

Background:

Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.

Objective:

An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.

Results:

The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.

Conclusion:

This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.

Mise en œuvre d’un test diagnostique permettant en Ontario l’analyse d’un panel de plusieurs gènes liés à l’épilepsie.Contexte:L’épilepsie demeure un trouble neurologique fréquent dont la prédisposition génétique apparaît notable. L’émergence du séquençage de nouvelle génération (SNG) a aussi transformé les tests génétiques en permettant un dépistage rapide des variantes causales que l’on retrouve dans de nombreux gènes. À l’heure actuelle, il n’existe pas, pour l’épilepsie, de tests diagnostiques homologués qui permettent en Ontario l’analyse d’un panel de gènes en vertu du SNG. Les échantillons de patients admissibles sont alors envoyés à l’extérieur du Canada afin d’être analysés par des laboratoires commerciaux, ce qui pèse lourd dans les budgets des systèmes publics de santé. Objectif : Un groupe de travail formé d’experts (généticiens médicaux, neurologues pédiatriques et spécialistes en épileptologie, généticiens biochimiques et généticiens moléculaires cliniques) a été formé par le service des laboratoires et de la génétique des ministères de la Santé et des Soins de Longue durée de l’Ontario afin d’élaborer une démarche programmatique visant à mettre en œuvre des tests diagnostiques basés sur un panel de plusieurs gènes. Ces tests seraient ensuite reconnus à titre de service public. Résultats:En matière de dépistage, ce groupe de travail a ainsi émis plusieurs recommandations visant à accompagner la prestation clinique en Ontario. Tout d’abord, un programme s’inspirant du projet « ECHO » (Extension of Community Healthcare Outcomes) devrait être ajouté dans le but de renseigner et de sensibiliser les prestataires de soins de santé qui demandent et qui interprètent ces tests basés sur un panel de plusieurs gènes. Ensuite, tout test de ce type doit reposer sur des preuves et tenir compte d’une panoplie d’indications cliniques afin de réduire les possibilités d’incertitude et de résultats secondaires. Enfin, il a été recommandé de procéder à un processus continu d’évaluation pour s’assurer que ces tests puissent être améliorés dans le futur. Conclusion:Ce plan de mise en œuvre de tests basés sur un panel de plusieurs gènes deviendra un modèle pour les soins destinés à un ensemble spécifique de problèmes de santé en Ontario. Outre l’épilepsie, il pourra servir comme prototype pour le dépistage d’autres maladies hétérogènes sur le plan génétique.

Copyright

Corresponding author

Correspondence to: Dr. David Dyment, Children’s Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario, Canada. Email: ddyment@cheo.on.ca

Footnotes

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These authors contributed equally to this manuscript.

Footnotes

References

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Implementation of Epilepsy Multigene Panel Testing in Ontario, Canada

  • David A. Dyment (a1) (a2), Asuri N. Prasad (a3), Kym M. Boycott (a1) (a2), Grace U. Ediae (a2), Taila Hartley (a2), Ayman Hassan (a4), Katherine E. Muir (a5), Murray Potter (a6), Lysa Boisse Lomax (a7), Olga Jarinova (a1) (a2), Bekim Sadikovic (a8) (a9), Dimitri J. Stavropoulos (a10) and O. Carter Snead (a11)...

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