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A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability

European Journal of Human Genetics volume 28, pages 1066–1077 (2020)Cite this article

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Abstract

Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients. Variant interpretation followed American College of Medical Genetics and Genomics (ACMG) guidelines. We demonstrate that WES, in combination with array-comparative genomic hybridisation, provides a diagnostic rate of 27% in unrelated adult epilepsy patients and 42% in unrelated paediatric patients. We observe a 2.7% rate of ACMG-defined incidental findings. Our findings indicate that WES has similar utility in both adult and paediatric cohorts and is appropriate for diagnostic testing in both epilepsy patient groups.

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Fig. 1: Pedigree chart for siblings 37 and 39 who carry an MBD5 variant, inherited from an unaffected mother with a somatic variant.

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Notes

  1. One of these CNVs (patient 84) awaits confirmation and segregation testing from accredited laboratory.

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Acknowledgements

This publication has emanated from research supported in part by eHealth Ireland, Health Service Executive (HSE), Grant Number 13/CDA/2223 and a research grant from Science Foundation Ireland (SFI) under Grant Number 16/RC/3948 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners. We thank Prof. Brendan Loftus and Catherine Moss of University College Dublin for access to sequencing platforms. We also thank the patients, their families, carers and clinical staff involved in the care of these patients for making this research possible.

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  1. These authors contributed equally: Norman Delanty, Gianpiero L. Cavalleri

Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, The Royal College of Surgeons in Ireland, Dublin, Ireland

    Katherine A. Benson, Maire White, Susan Byrne, Robert Carton, Elizabeth Comerford, Hany El-Naggar, Nisha Gangadharan, Sinéad Heavin, Hugh Kearney, Mark McCormack, Kevin Power, Mary Fitzsimons, Marie Greally, Norman Delanty & Gianpiero L. Cavalleri

  2. FutureNeuro SFI Research Centre, Dublin, Ireland

    Katherine A. Benson, Susan Byrne, Robert Carton, Hany El-Naggar, Nisha Gangadharan, Hugh Kearney, Kevin Power, Mary Fitzsimons, Norman Delanty & Gianpiero L. Cavalleri

  3. Department of Paediatrics, National University of Ireland Galway, Galway University Hospital, Galway, Ireland

    Nicholas M. Allen

  4. Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland

    Susan Byrne, Mary O’ Regan & David Webb

  5. Department of Neurology, Cork University Hospital & University College Cork, Cork, Ireland

    Daniel Costello & Brian Sweeney

  6. Department of Neurology, St James’ Hospital, Dublin, Ireland

    Colin Doherty

  7. Ergo IT Services, Dublin, Ireland

    Brendan Dunleavey

  8. Department of Neurology, Beaumont Hospital, Dublin, Ireland

    Hany El-Naggar, Hugh Kearney & Norman Delanty

  9. Congenica Ltd, Wellcome Genome Campus, Hinxton, Cambridge, UK

    Nicholas J. Lench, Anthony S. Rogers & Charles A. Steward

  10. Department of Neurology, University Hospital Galway, Galway, Ireland

    John Lynch

  11. Microsoft, Dublin, Ireland

    Karl Podesta

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Correspondence to Gianpiero L. Cavalleri.

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NJL, ASR and CAS are employed by Congenica Ltd.

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Benson, K.A., White, M., Allen, N.M. et al. A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability. Eur J Hum Genet 28, 1066–1077 (2020). https://doi.org/10.1038/s41431-020-0610-3

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