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

被引：40

作者：

Benson, Katherine A. ^{[1
,2
]}

White, Maire ^{[1
]}

Allen, Nicholas M. ^{[3
]}

Byrne, Susan ^{[1
,2
,4
]}

Carton, Robert ^{[1
,2
]}

Comerford, Elizabeth ^{[1
]}

Costello, Daniel ^{[5
,6
]}

Doherty, Colin ^{[7
]}

Dunleavey, Brendan ^{[8
]}

El-Naggar, Hany ^{[1
,2
,9
]}

Gangadharan, Nisha ^{[1
,2
]}

Heavin, Sinead ^{[1
]}

Kearney, Hugh ^{[1
,2
,9
]}

Lench, Nicholas J. ^{[10
]}

Lynch, John ^{[11
]}

McCormack, Mark ^{[1
]}

O'Regan, Mary ^{[4
]}

Podesta, Karl ^{[12
]}

Power, Kevin ^{[1
,2
]}

Rogers, Anthony S. ^{[10
]}

Steward, Charles A. ^{[10
]}

Sweeney, Brian ^{[5
,6
]}

Webb, David ^{[4
]}

Fitzsimons, Mary ^{[1
,2
]}

Greally, Marie ^{[1
]}

Delanty, Norman ^{[1
,2
,9
]}

Cavalleri, Gianpiero L. ^{[1
,2
]}

机构：

[1] Royal Coll Surgeons Ireland, Sch Pharm & Biomol Sci, Dublin, Ireland

[2] FutureNeuro SFI Res Ctr, Dublin, Ireland

[3] Natl Univ Ireland Galway, Galway Univ Hosp, Dept Paediat, Galway, Ireland

[4] Our Ladys Childrens Hosp Crumlin, Dublin, Ireland

[5] Cork Univ Hosp, Dept Neurol, Cork, Ireland

[6] Univ Coll Cork, Cork, Ireland

[7] St James Hosp, Dept Neurol, Dublin, Ireland

[8] Ergo IT Serv, Dublin, Ireland

[9] Beaumont Hosp, Dept Neurol, Dublin, Ireland

[10] Congenica Ltd, Wellcome Genome Campus, Hinxton, Cambs, England

[11] Univ Hosp Galway, Dept Neurol, Galway, Ireland

[12] Microsoft, Dublin, Ireland

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2020年 / 28卷 / 08期

基金：

爱尔兰科学基金会;

关键词：

DE-NOVO MUTATIONS; REPORTING INCIDENTAL FINDINGS; COPY NUMBER VARIATION; MEDICAL GENETICS; AMERICAN-COLLEGE; ACMG RECOMMENDATIONS; CLINICAL EXOME; ENCEPHALOPATHY; VARIANTS; ASSOCIATION;

D O I：

10.1038/s41431-020-0610-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1066 / 1077

页数：12

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