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


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


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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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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 (2020). https://doi.org/10.1038/s41431-020-0610-3

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