The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies
Open accessAbstract
Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2; chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7; P = 0.009). Including nine patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“a review of reported data from control cohorts (n = 66,462 subjects) summarized to date show that about 0.25% of controls are found with the 15q11.2 BP1–BP2 microdeletion [18,27,28,29,30,31].”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [29]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The medical literature surrounding this microdeletion syndrome and seizures indicate that this chromosomal anomaly may be a risk factor for epilepsy [29,41,42,43].”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [29]
The cited source says what the claim attributes to it.
In the citing paper
“epilepsy (OR 4.9)4”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [4]
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
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795
McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236
Structural Variation of Chromosomes in Autism Spectrum Disorder
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.009 · Cited by 1,815 · cited 3×
“2 was based on previous large-scale copy number variation analyses (1q21.1: Brunetti-Pierri et al., 2008; Mefford et al., 2008; Schizophrenia Consortium, 2008; Stefansson et al., 2008; Need et al., 2009; 15q11.2: Stefansson et al., 2008; Kirov et al., 2009; 16p11.2: Sebat et al., 2007; Kumar et al., 2008; Marshall et…”
BackgroundMethodSelf-citationLarge recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745
Association between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa075974 · Cited by 1,666
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
Mechanisms of change in gene copy number
Hastings, P. J., Lupski, J. R., Rosenberg, S. M., & Ira, G. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2593 · Cited by 1,316
Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., Huang, S., Maloney, V. K., Crolla, J. A., Baralle, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0805384 · Cited by 804
Self-citationMechanisms for human genomic rearrangements
Gu, W., Zhang, F., & Lupski, J. R. (2008) · PathoGenetics · doi:10.1186/1755-8417-1-4 · Cited by 744
Recurrent 16p11.2 microdeletions in autism
Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., Gilliam, T. C., Nowak, N. J., Cook, E. H., Dobyns, W. B., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm376 · Cited by 731
Copy-number variations associated with neuropsychiatric conditions
Cook Jr, E. H., & Scherer, S. W. (2008) · Nature · doi:10.1038/nature07458 · Cited by 659
Brunetti-Pierri, N., Berg, J. S., Scaglia, F., Belmont, J., Bacino, C. A., Sahoo, T., Lalani, S. R., Graham, B., Lee, B., Shinawi, M., et al. (2008) · Nature Genetics · doi:10.1038/ng.279 · Cited by 625
Population analysis of large copy number variants and hotspots of human genetic disease
Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.12.014 · Cited by 591
Self-citationA recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures.
Sharp, A. J., Mefford, H. C., Li, K., Baker, C., Skinner, C., Stevenson, R. E., Schroer, R. J., Novara, F., De Gregori, M., Ciccone, R., et al. (2008) · Nature Genetics · doi:10.1038/ng.93 · Cited by 582
Self-citation15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.
Helbig, I., Mefford, H. C., Sharp, A. J., Guipponi, M., Fichera, M., Franke, A., Muhle, H., de Kovel, C., Baker, C., von Spiczak, S., et al. (2009) · Nature Genetics · doi:10.1038/ng.292 · Cited by 551
Self-citationCellular and Network Mechanisms of Spike‐Wave Seizures
Blumenfeld, H. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00311.x · Cited by 455
A Genome-Wide Investigation of SNPs and CNVs in Schizophrenia
Need, A. C., Ge, D., Weale, M. E., Maia, J. M., Feng, S., Heinzen, E. L., Shianna, K. V., Yoon, W., Kasperavičiūtė, D., Gennarelli, M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000373 · Cited by 454
Miller, D. T., Shen, Y., Weiss, L. A., Korn, J., Anselm, I., Bridgemohan, C., Cox, G. F., Dickinson, H., Gentile, J., Harris, D. J., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.059907 · Cited by 427
KORA-gen - Resource for Population Genetics, Controls and a Broad Spectrum of Disease Phenotypes
Wichmann, H. ‐., Gieger, C., & Illig, T. (2005) · Das Gesundheitswesen · doi:10.1055/s-2005-858226 · Cited by 417
Self-citationSupport for the involvement of large copy number variants in the pathogenesis of schizophrenia.
Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Craddock, N., Owen, M. J., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp043 · Cited by 390
Epidemiology of Idiopathic Generalized Epilepsies
Jallon, P., & Latour, P. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00309.x · Cited by 371
van Bon, B. W. M., Mefford, H. C., Menten, B., Koolen, D. A., Sharp, A. J., Nillesen, W. M., Innis, J. W., de Ravel, T. J. L., Mercer, C. L., Fichera, M., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.063412 · Cited by 363
Self-citationHannes, F., Sharp, A. J., Mefford, H. C., de Ravel, T. J. L., Ruivenkamp, C. A. L., Breuning, M. H., Fryns, J., Devriendt, K., Buggenhout, G. V., Vogels, A., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2007.055202 · Cited by 348
Self-citationKrawczak, M., Nikolaus, S., von Eberstein, H., Croucher, P. J. P., Mokhtari, N. E. E., & Schreiber, S. (2006) · Public Health Genomics · doi:10.1159/000090694 · Cited by 338
Self-citationUllmann, R., TURNER, G. M., Kirchhoff, M., Chen, W., Tonge, B. J., Rosenberg, C., Field, M., Vianna‐Morgante, A. M., Christie, L., Krepischi, A. C. V., et al. (2007) · Human Mutation · doi:10.1002/humu.20546 · Cited by 292
Navigating the channels and beyond: unravelling the genetics of the epilepsies
Helbig, I., Scheffer, I. E., Mulley, J. C., & Berkovic, S. F. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70039-5 · Cited by 281
Self-citationDibbens, L. M., Mullen, S. A., Helbig, K. L., Mefford, H. C., Bayly, M. A., Bellows, S. T., Leu, C., Trucks, H., Obermeier, T., Wittig, M., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp311 · Cited by 268
Self-citationNovel microdeletion syndromes detected by chromosome microarrays
Slavotinek, A. M. (2008) · Human Genetics · doi:10.1007/s00439-008-0513-9 · Cited by 259
Duplication hotspots, rare genomic disorders, and common disease
Mefford, H. C., & Eichler, E. E. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.003 · Cited by 208
Self-citationMechanisms of human inherited epilepsies
Reid, C. A., Berkovic, S. F., & Petrou, S. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.09.016 · Cited by 207
A 15q13.3 microdeletion segregating with autism
Pagnamenta, A. T., Wing, K., Akha, E. S., Knight, S. J. L., Bölte, S., Schmötzer, G., Duketis, E., Poustka, F., Klauck, S. M., Poustka, A., et al. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.228 · Cited by 177
Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome
Bassett, A. S., Marshall, C. R., Lionel, A. C., Chow, E. W. C., & Scherer, S. W. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn307 · Cited by 162
Emerging themes and new challenges in defining the role of structural variation in human disease
Sharp, A. J. (2008) · Human Mutation · doi:10.1002/humu.20843 · Cited by 124
Lis1–Nde1-dependent neuronal fate control determines cerebral cortical size and lamination
Pawlisz, A. S., Mutch, C. A., Wynshaw-Boris, A. J., Chenn, A., Walsh, C. A., & Feng, Y. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn144 · Cited by 90
Hennah, W., & Porteous, D. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004906 · Cited by 80
Population Analysis of Large Copy Number Variants and Hotspots of Human Genetic Disease
Itsara, A., Cooper, G. M., Baker, C. A., Girirajan, S., Li, J. Z., Absher, D., Krauss, R. M., Myers, R., Ridker, P. M., Chasman, D. I., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.008 · Cited by 40
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- 2005, 46, 21
- 2005, 46, 10
Cited by
Sorted by citations
Miller, D. T., Adam, M. P., Aradhya, S., Biesecker, L. G., Brothman, A. R., Carter, N. P., Church, D. M., Crolla, J. A., Eichler, E. E., Epstein, C. J., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.04.006 · Cited by 2,882
Self-citationAnalysis of shared heritability in common disorders of the brain
The Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G. J., Gormley, P., et al. (2018) · Science · doi:10.1126/science.aap8757 · Cited by 1,924
Self-citationExome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203
Self-citationDevinsky, O., Vezzani, A., O'Brien, T. J., Jetté, N., Scheffer, I. E., de Curtis, M., & Perucca, P. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.24 · Cited by 998
Rare de novo and transmitted copy-number variation in autistic spectrum disorders
Levy, D., Ronemus, M., Yamrom, B., Lee, Y.-H., Leotta, A., Kendall, J., Marks, S., Lakshmi, B., Pai, D., Ye, K., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.015 · Cited by 712
Metadata
- Authors
- de Kovel, C. G. F., Trucks, H., Helbig, I., Mefford, H. C., Baker, C., Leu, C., Kluck, C., Muhle, H., von Spiczak, S., Ostertag, P., Obermeier, T., Kleefuss-Lie, A. A., Hallmann, K., Steffens, M., Gaus, V., Klein, K. M., Hamer, H. M., Rosenow, F., Brilstra, E. H., Kasteleijn-Nolst Trenite, D., Swinkels, M. E. M., Weber, Y. G., Unterberger, I., Zimprich, F., Urak, L., Feucht, M., Fuchs, K., Moller, R. S., Hjalgrim, H., De Jonghe, P., Suls, A., Ruckert, I.-M., Wichmann, H.-E., Franke, A., Schreiber, S., Nurnberg, P., Elger, C. E., Lerche, H., Stephani, U., Koeleman, B. P. C., Lindhout, D., Eichler, E. E., & Sander, T.
- Affiliations
- University Medical Center Utrecht (NL)
- University of Cologne (DE)
- University of Washington (US)
- University Hospital Schleswig-Holstein (DE)
- University of Bonn (DE)
- Humboldt-Universität zu Berlin (DE)
- Philipps University of Marburg (DE)
- Universität Ulm (DE)
- Innsbruck Medical University (AT)
- Medical University of Vienna (AT)
- University of Antwerp (BE)
- Helmholtz Munich (DE)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-10-20
- Volume
- 133
- Issue
- 1
- Pages
- 23-32
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2801323
- OpenAlex
- W2154259233
- Cited by
- 445
- References
- 38
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 19 · 2023: 16 · 2022: 17 · 2021: 12 · 2020: 21 · 2019: 18 · 2018: 20 · 2017: 30 · 2016: 23 · 2015: 45 · 2014: 41 · 2013: 50 · 2012: 42
- FWCI
- 23.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Danish Cancer Society Research Center
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung (01GS08120, 01GS08123)
- Fonds De La Recherche Scientifique - FNRS
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (917.66.315)
- Exzellenzclusters Entzündungsforschung
- Vlaamse regering
- National Institutes of Health
- 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
- idiopathic generalized epilepsy, 15q11.2, 1q21.1, 16p11.2, 22q11.2, genetic risk, structural variants, epileptogenesis, genetic susceptibility, single nucleotide polymorphism array
- MeSH terms
- Adolescent, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 16, Epilepsy, Generalized, Female, Humans, Male, Pedigree, Cohort Studies, Genetic Predisposition to Disease, Young Adult
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
