Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1

Carvill, Gemma L., Heavin, Sinéad B., Yendle, Simone C., McMahon, Jacinta M., O'Roak, Brian J., Cook, Joseph, Khan, Adiba, Dorschner, Michael O., Weaver, Molly, Calvert, Sophie, Malone, Stephen, Wallace, Geoffrey, Stanley, Thorsten, Bye, Ann M. E., Bleasel, Andrew, Howell, Katherine B., Kivity, Sara, Mackay, Mark T., Rodriguez-Casero, Victoria, Webster, Richard, Korczyn, Amos, Afawi, Zaid, Zelnick, Nathanel, Lerman-Sagie, Tally, Lev, Dorit, Møller, Rikke S., Gill, Deepak, Andrade, Danielle M., Freeman, Jeremy L., Sadleir, Lynette G., Shendure, Jay, Berkovic, Samuel F., Scheffer, Ingrid E. and Mefford, Heather C. (2013) Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nature Genetics, 45 7: 825-830. doi:10.1038/ng.2646

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Author Carvill, Gemma L.
Heavin, Sinéad B.
Yendle, Simone C.
McMahon, Jacinta M.
O'Roak, Brian J.
Cook, Joseph
Khan, Adiba
Dorschner, Michael O.
Weaver, Molly
Calvert, Sophie
Malone, Stephen
Wallace, Geoffrey
Stanley, Thorsten
Bye, Ann M. E.
Bleasel, Andrew
Howell, Katherine B.
Kivity, Sara
Mackay, Mark T.
Rodriguez-Casero, Victoria
Webster, Richard
Korczyn, Amos
Afawi, Zaid
Zelnick, Nathanel
Lerman-Sagie, Tally
Lev, Dorit
Møller, Rikke S.
Gill, Deepak
Andrade, Danielle M.
Freeman, Jeremy L.
Sadleir, Lynette G.
Shendure, Jay
Berkovic, Samuel F.
Scheffer, Ingrid E.
Mefford, Heather C.
Title Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Formatted title
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2013-07
Sub-type Article (original research)
DOI 10.1038/ng.2646
Open Access Status
Volume 45
Issue 7
Start page 825
End page 830
Total pages 6
Place of publication United States
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
Keyword Autism spectrum disorders
Intellectual disability
Sodium-channel
Mental-retardation
Gene Scn2A
Microdeletion
Seizures
Epilepsies
Phenotype
Deletions
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 163 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 171 times in Scopus Article | Citations
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