CoChat
Sign Up
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

Open access
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
Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pgen.1000962

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

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

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 61 references

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

Cited by

Sorted by citations

Related

See all

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review