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15q13.3 microdeletions increase risk of idiopathic generalized epilepsy


We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 × 10−8). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.

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Figure 1: Confirmation of 15q13.3 microdeletions using custom array CGH.


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We thank all the subjects and their families for participating in this study. We are also grateful to H. Bode for referral of subjects and A. Ackerhans and K. Moldenhauer for database management. This study used samples from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (, as well as clinical data. NINDS Repository sample numbers corresponding to the samples used are available upon request. This study was supported by grants from the German Research Foundation (SA434/4-1, T.S., P.N.), the German Federal Ministry of Education and Research (National Genome Research Network, NGFN-2: NeuroNet, NGFNplus: EMINet), the European Community (FP6 Integrated Project EPICURE, LSHM-CT-2006-037315; grant agreement 219250, A.J.S.), the PopGen biobank, the University of Kiel (I.H.), the Danish National Research Foundation (R.S.M.), in part by grants from the NIH (HD043569, E.E.E.), the National Epilepsy Funds (NEF, grant no. 04-08, B.P.C.K., D. Lindhout), the Netherlands Organization for Scientific Research (NOW, grant no. 917.66.315, B.P.C.K., C.d.K.) and the German Research Foundation/German Federal Ministry of Education and Research (DFG/BMBF) excellence cluster “Inflammation at Interfaces” (A.F., M.W., S.S.). E.E.E. is an investigator of the Howard Hughes Medical Institute.

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T.S. and E.E.E. initiated and designed the study; I.H., H.M., S.v.S., I.S., A.A.K.-L., V.G., B.S., K.M.K., P.S.R., F.R., Y.W., H.L., F.Z., L.U., K.F., M. Feucht, F.V., G.-J.d.H., R.S.M., H.H., D. Luciano, C.R., D. Lindhout, C.E.E., U.S. and T.S. recruited and phenotyped the EPICURE sample; H.C.M., A.J.S., M.G., M. Fichera, C.B., P.G., P.T., A.M. and E.E.E. recruited and phenotyped the mixed IGE sample; A.F., M.W., M.N. and S.S. recruited and phenotyped the PopGen control sample; I.H., A.F., C.L., K.L.K., I.S., M.W., M.N., P.N. and T.S. performed the CNV analysis on SNP arrays; H.C.M., A.J.S., M. Fichera, C.B. and D. Luciano performed the qPCR screening; H.C.M., M. Fichera, C.B. and D. Luciano performed the screening using Illumina Genotyping BeadChips; H.C.M., A.J.S. and C.B. performed the confirmation using NimbleGen arrays; C.d.K., B.P.C.K. and D. Lindhout performed the confirmation using Illumina CNV BeadChips; I.H., H.C.M., A.J.S., M.G., M. Fichera, A.F., C.d.K., K.L.K., C.R., B.P.C.K., D. Lindhout, E.E.E. and T.S. coordinated the work and prepared the manuscript.

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Correspondence to Thomas Sander.

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Supplementary Methods, Supplementary Table 1 and Supplementary Figures 1–3 (PDF 2203 kb)

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Helbig, I., Mefford, H., Sharp, A. et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41, 160–162 (2009).

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