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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.
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“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]
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“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]
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“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]
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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
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Items 401–446 of 446
Genetic risk factors for amyotrophic lateral sclerosis : focusing on copy number variation
Blauw, H. M. (2012) · Utrecht University Repository (Utrecht University)
The Mutational Spectrum of Neurodevelopmental Disorders
Merner, N. D., Dion, P. A., & Rouleau, G. A. (2015) · Wiley eBooks · doi:10.1002/9781118524947.ch3
Poot, M. (2013) · Molecular Syndromology · doi:10.1159/000355850
Current Tools for Interpretation of Genomic Copy Number Variants
Noor, A., & Stavropoulos, D. J. (2015) · Current Genetic Medicine Reports · doi:10.1007/s40142-015-0078-6
epilepsy with intellectual disability Copy number variants are frequent in genetic generalized
Mullen, S. A., Carvill, G. L., & Bellows, S. T. (2013)
schizophrenia-associated loci Analysis of copy number variations at 15
O’Donovan, M. C., Owen, M. J., Richards, A. L., Mahoney‐Davies, G., Legge, S. E., Moran, J. L., Walters, J., Georgieva, L., Isles, A. R., & Chambert, K. D. (2014)
Mikrodeletionen 15q13.3, 16p13.11 und 15q11.2 in Epilepsien des Kindes- und Jugendalters
Obermeier, T. (2015) · MACAU: Open Access Repository of Kiel University (University Library Kiel)
Self-citationGenetic Aspects of Human Epilepsy
Prasad, A. N., & Prasad, C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00122-1
Nuevo caso de disfunción neurológica y microdeleción 15q11.2
Santotoribio, J. D., Salinas-Martín, M. V., & Batalha-Caetano, P. (2015) · Medicina Clínica · doi:10.1016/j.medcli.2014.11.006
Kurul, S. H. (2016) · Turkiye Klinikleri Journal of Pediatrics · doi:10.5336/pediatr.2015-48619
Torticollis in 15q11.2 Microdeletion Syndrome: a Rare Association in Angelman-like Syndromes
Szabó, T. M., Újfalusi, A., & Bessenyei, B. (2016) · Journal of Genetic Syndromes & Gene Therapy · doi:10.4172/2157-7412.1000294
Vianna, G. S., de Freitas, M. L., de Oliveira, V. T., Pietra, R. X., Gonçalves, M. D. S., Rocha, P. P. O., Monteiro, R. A. C., Ferreira, L. C. D. A., Xavier, R. R., Carvalho, A. M., et al. (2016) · Molecular Syndromology · doi:10.1159/000450631 · Cited by 1
Neurological dysfunction and 15q11.2 microdeletion: Report of a new case
Santotoribio, J. D., Salinas-Martín, M. V., & Batalha-Caetano, P. (2015) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2016.02.046
Babameto-Laku, A., Grabova, S., Kruja, J., & Vyshka, G. (2017) · Journal of Pediatric Epilepsy · doi:10.1055/s-0037-1603493
Molecular Diagnosis of Epilepsy in Clinical Practice
이윤정, 권순학, 황수경, & An, J.-H. (2016) · Annals of Child Neurology · doi:10.26815/jkcns.2016.24.4.183
Pérez‐Palma, E., Helbig, I., Klein, K. M., Anttila, V., Horn, H., Reinthaler, E. M., Gormley, P., Ganna, A., Byrnes, A., Pernhorst, K., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/131359
Self-citationFinding the Missing Pieces: The Microdeletion Burden in GGE
Mefford, H. C. (2016) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7597-16.1.16
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Wolking, S., & Lerche, H. (2019) · Nervenheilkunde · doi:10.1055/a-0952-6908
Self-citation[Genetic variations and epilepsy].
Sun, Y., & Yin, F. (2017) · PubMed Central · doi:10.7499/j.issn.1008-8830.2017.09.002
15q11.2 Deletion Syndrome: Expanding the Phenotype
(2020) · International Journal of Case Reports · doi:10.28933/ijcr-2020-09-1105
Guarnaccia, M., Naimo, G. D., Conforti, F. L., & Cavallaro, S. (2020) · Journal of Clinical and Molecular Medicine · doi:10.15761/jcmm.1000133
Genome-wide Investigation of Rare Genetic Variation in Epilepsy and Autism Spectrum Disorder
Qaiser, F. (2020) · TSpace (University of Toronto)
Genetic Counselling in Epilepsy
Zara, F. (2015) · Wiley eBooks · doi:10.1002/9781118936979.ch24
Stier, C. (2022) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9165
Recurrent febrile seizures led to the diagnosis of 22q11.2 deletion syndrome in a 12-year-old boy
Takiyama, Y., Jogamoto, T., Eguchi‐Ishimae, M., Nagatani, K., & Eguchi, M. (2022) · Epilepsy & Seizure · doi:10.3805/eands.14.51
Pérez‐Palma, E., Niestroj, L., Inca‐Martinez, M., Villamán, C., Sarihan, E. I., Lal, D., & Mata, I. F. (2022) · Neuromethods · doi:10.1007/978-1-0716-2357-2_10
Belousova, E. D., Iourov, I. Y., Shulyakova, I. V., & Tsyshkova, O. N. (2014) · Journal of Neurology and Epidemiology · doi:10.12974/2309-6179.2014.01.01.8
Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy
Lin, Z.-J., Huang, B., Su, L.-F., Zhu, S.-Y., He, J., Chen, G., & Lin, P.-X. (2023) · Neurogenetics · doi:10.1007/s10048-023-00715-x
Baumgartner, C., Asamoah-Akwonu, L., Koren, J. P., Lang, C., & Pirker, S. (2023) · Klinische Neurophysiologie · doi:10.1055/a-2132-9596
Lawrence, C. J., Kernohan, K. D., & Dyment, D. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99417-0.00029-x
Bonkowski, E. S., & Mefford, H. C. (2024) · Oxford University Press eBooks · doi:10.1093/med/9780197549469.003.0041
Self-citationMeossi, C., Carrer, A., Ciaccio, C., Pezzoli, L., Pezzani, L., Silipigni, R. M., Sciacca, F. L., Tenconi, R., Esposito, S., Laurentiis, A. D., et al. (2024) · Genes · doi:10.3390/genes15111441
Han, J. Y., Kim, T. Y., & Park, J. (2024) · Biomedicines · doi:10.3390/biomedicines12122663
Irelli, E. C., Fanella, M., Chaumette, B., Putotto, C., Mignot, C., Mazzeo, A., Lemke, J. R., Riva, A., Accinni, T., Louveau, C., et al. (2024) · Epilepsia · doi:10.1111/epi.18220
Prevalence of Etiological Factors in Adult Patients With Epilepsy in Herzegovina
Pejanović-Škobić, N., Hodžić, A., Pravdić, N., Bender, M., & Kordic, J. (2025) · Cureus · doi:10.7759/cureus.82184
Fehlende Erblichkeit bei genetisch komplexen Erkrankungen
Neubauer, B. A., & Klein, K. M. (2014) · Clinical Epileptology · doi:10.1007/s10309-013-0351-1
Self-citationSisodiya, S. M. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-382227-7.00087-2
Additional file 1 of Rare copy-number variants as modulators of common disease susceptibility
Auwerx, C., Jõeloo, M., Sadler, M. C., Tesio, N., Ojavee, S., Clark, C. J., Mägi, R., Reymond, A., & Kutalik, Z. (2024) · Figshare · doi:10.6084/m9.figshare.24955993
Additional file 3 of Rare copy-number variants as modulators of common disease susceptibility
Auwerx, C., Jõeloo, M., Sadler, M. C., Tesio, N., Ojavee, S., Clark, C. J., Mägi, R., Reymond, A., & Kutalik, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26664211
Additional file 2 of Rare copy-number variants as modulators of common disease susceptibility
Auwerx, C., Jõeloo, M., Sadler, M. C., Tesio, N., Ojavee, S., Clark, C. J., Mägi, R., Reymond, A., & Kutalik, Z. (2024) · Figshare · doi:10.6084/m9.figshare.24956204
Tang, X., Su, J., Li, W., Zhou, C., Wei, Y., Lu, W., Wang, L., Li, J., Zhang, S., Chen, F., et al. (2025) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-025-08467-2
Młynek, M., Wicher, D., Cieślikowska, A., Urbańska, K., Przywoźna-Zduńczyk, K., Zawadzka-Więch, U., Markowska-Krawczyk, K., Bal, A., Purwin, S., Sielska-Rotblum, D., et al. (2026) · Genes · doi:10.3390/genes17030256
Derhourhi, M. (2018) · theses.fr (ABES) · doi:10.70675/2d396fe9z564dz48a1z89b4z746f99df764e
Chin, H. L., Chang, J., & Nordli, D. R. (2026) · Epileptic Disorders · doi:10.1002/epd2.70328
Genotype-phenotype studies in rare chromosome aberrations
Feenstra, I. (2013) · Radboud Repository (Radboud University)
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
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