Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies

Heather C Mefford; Hiltrud Muhle; Philipp Ostertag; Sarah von Spiczak; Karen Buysse; Carl Baker; Andre Franke; Alain Malafosse; Pierre Genton; Pierre Thomas; Christina A Gurnett; Stefan Schreiber; Alexander G Bassuk; Michel Guipponi; Ulrich Stephani; Ingo Helbig; Evan E Eichler

doi:10.1371/journal.pgen.1000962

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Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies

Journal article

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Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies

Heather C Mefford, Hiltrud Muhle, Philipp Ostertag, Sarah von Spiczak, Karen Buysse, Carl Baker, Andre Franke, Alain Malafosse, Pierre Genton, Pierre Thomas, …

PLoS genetics, Vol.6(5), pp.e1000962-e1000962

05/20/2010

DOI: 10.1371/journal.pgen.1000962

PMCID: PMC2873910

PMID: 20502679

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Abstract

Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy.

Genetic Variation

Epilepsy - genetics

Genetic Predisposition to Disease

Gene Dosage

Genome

Humans

Details

Title: Subtitle: Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies
Creators: Heather C Mefford - Department of Pediatrics, University of Washington, Seattle, Washington, United States of America. hmefford@u.washington.edu
Hiltrud Muhle
Philipp Ostertag
Sarah von Spiczak
Karen Buysse
Carl Baker
Andre Franke
Alain Malafosse
Pierre Genton
Pierre Thomas
Christina A Gurnett
Stefan Schreiber
Alexander G Bassuk
Michel Guipponi
Ulrich Stephani
Ingo Helbig
Evan E Eichler
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.6(5), pp.e1000962-e1000962
DOI: 10.1371/journal.pgen.1000962
PMID: 20502679
PMCID: PMC2873910
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: Public Library Science; United States
Grant note: R01 NS064159 / NINDS NIH HHS\nHoward Hughes Medical Institute\nNS064159 / NINDS NIH HHS\nK12 HD043376 / NICHD NIH HHS\nHD043376 / NICHD NIH HHS\nR01 HD043569 / NICHD NIH HHS\nHD043569 / NICHD NIH HHS
Language: English
Date published: 05/20/2010
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020503102771

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