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Cited by 474Genomic variations and chromosomal abnormalitiesEpilepsy research and treatmentGenetics and Neurodevelopmental Disorders

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Genome-Wide Copy Number Variation in Epilepsy: Novel Susceptibility Loci in Idiopathic Generalized and Focal Epilepsies

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Mefford, Heather C., Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Buysse, Karen, Baker, Carl, Franke, Andre, Malafosse, Alain, Genton, Pierre, Thomas, Pierre, Gurnett, Christina A., Schreiber, Stefan, Bassuk, Alexander G., Guipponi, Michel, Stephani, Ulrich, Helbig, Ingo, Eichler, Evan E.·2010·PLoS Genetics
DOI 10.1371/journal.pgen.1000962PMC PMC2873910
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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.

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Crossref · 10.1371/journal.pgen.1000962

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Figures

Figure 1 Deletions and duplications at genomic rearrangement hotspots in 20 probands. Array CGH results are depicted for (A) 15q13.3, chr15: 28.0–31.0 Mb, (B) 16p13.11, chr16: 14.5–18.5 Mb, (C) 15q11.2, chr15: 20.0–20.9 Mb, (D) 1q21.1, chr1: 144.0–147.5 Mb, (E) 16p12.1, chr16: 21.6–22.6 Mb, (F) 16p11.2, chr16:28.6–29.1 Mb, and (G) 16p11.2, chr16: 29.0–30.3 Mb. For each individual, deviations of probe log2 ratios from 0 are depicted by gray and black lines. Those exceeding a threshold of 1.5 s.d. from the mean probe ratio are colored green and red to represent relative gains and losses, respectively. Segmental duplications of increasing similarity (90–98%, 98–99%, and >99%) are represented by gray, yellow, and orange bars, respectively. RefSeq genes are depicted in blue.
Figure 1 Deletions and duplications at genomic rearrangement hotspots in 20 probands. Array CGH results are depicted for (A) 15q13.3, chr15: 28.0–31.0 Mb, (B) 16p13.11, chr16: 14.5–18.5 Mb, (C) 15q11.2, chr15: 20.0–20.9 Mb, (D) 1q21.1, chr1: 144.0–147.5 Mb, (E) 16p12.1, chr16: 21.6–22.6 Mb, (F) 16p11.2, chr16:28.6–29.1 Mb, and (G) 16p11.2, chr16: 29.0–30.3 Mb. For each individual, deviations of probe log2 ratios from 0 are depicted by gray and black lines. Those exceeding a threshold of 1.5 s.d. from the mean probe ratio are colored green and red to represent relative gains and losses, respectively. Segmental duplications of increasing similarity (90–98%, 98–99%, and >99%) are represented by gray, yellow, and orange bars, respectively. RefSeq genes are depicted in blue.CC BY · PubMed Central
Figure 2 Two rare CNVs in five probands. Array CGH results are shown for the for two rare CNVs detected in probands EMJ071 (A), ND05260 (B), EPI51 (C), K034 (D), and EMJ117 (E). Array CGH results are depicted as in Figure 1; segmental duplications are not shown in this figure.
Figure 2 Two rare CNVs in five probands. Array CGH results are shown for the for two rare CNVs detected in probands EMJ071 (A), ND05260 (B), EPI51 (C), K034 (D), and EMJ117 (E). Array CGH results are depicted as in Figure 1; segmental duplications are not shown in this figure.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. I Helbig, 2009, 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy., Nat Genet, 41, 160, 10.1038/ng.292 · DOI · Paper page

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Metadata

Authors
Mefford, H. C., Muhle, H., Ostertag, P., von Spiczak, S., Buysse, K., Baker, C., Franke, A., Malafosse, A., Genton, P., Thomas, P., Gurnett, C. A., Schreiber, S., Bassuk, A. G., Guipponi, M., Stephani, U., Helbig, I., & Eichler, E. E.
Affiliations
  • University of Washington (US)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • Ghent University Hospital (BE)
  • University of Geneva (CH)
  • Henri Gastaut Hospital (FR)
  • Hôpital Pasteur (FR)
  • Washington University in St. Louis (US)
  • University of Iowa (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Mefford, Heather C.
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2010-05-20
Volume
6
Issue
5
Pages
e1000962
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1000962
PMC
PMC2873910
OpenAlex
W2003479128
Cited by
474
References
61
Citations by year
2026: 8 · 2025: 6 · 2024: 17 · 2023: 7 · 2022: 20 · 2021: 33 · 2020: 21 · 2019: 21 · 2018: 16 · 2017: 28 · 2016: 22 · 2015: 48 · 2014: 45 · 2013: 61 · 2012: 51
FWCI
32.35
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Howard Hughes Medical Institute
  • Burroughs Wellcome Fund
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS064159, NS064159)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD043376, HD043569, K12HD043376, R01HD043569)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
copy number variation, epilepsy, idiopathic generalized epilepsy, focal epilepsy, AUTS2, CNTNAP2, 15q11.2, 15q13.3, neurodevelopmental disorders, intellectual disability, autism spectrum disorder, schizophrenia
MeSH terms
Epilepsy, Humans, Genetic Variation, Genome, Gene Dosage, Genetic Predisposition to Disease

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