TY - JOUR
T1 - A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability
AU - Benson, Katherine A.
AU - White, Maire
AU - Allen, Nicholas M.
AU - Byrne, Susan
AU - Carton, Robert
AU - Comerford, Elizabeth
AU - Costello, Daniel
AU - Doherty, Colin
AU - Dunleavey, Brendan
AU - El-Naggar, Hany
AU - Gangadharan, Nisha
AU - Heavin, Sinéad
AU - Kearney, Hugh
AU - Lench, Nicholas J.
AU - Lynch, John
AU - McCormack, Mark
AU - Regan, Mary O’
AU - Podesta, Karl
AU - Power, Kevin
AU - Rogers, Anthony S.
AU - Steward, Charles A.
AU - Sweeney, Brian
AU - Webb, David
AU - Fitzsimons, Mary
AU - Greally, Marie
AU - Delanty, Norman
AU - Cavalleri, Gianpiero L.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to European Society of Human Genetics.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85083247742
U2 - 10.1038/s41431-020-0610-3
DO - 10.1038/s41431-020-0610-3
M3 - Article
SN - 1018-4813
VL - 28
SP - 1066
EP - 1077
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -