Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

15q13.3 microdeletions increase risk of idiopathic generalized epilepsy

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

References

  1. Jallon, P. & Latour, P. Epilepsia 46 (Suppl. 9), 10–14 (2005).

    Article  Google Scholar 

  2. Ottman, R. Epilepsia 46 (Suppl. 10), 7–14 (2005).

    Article  Google Scholar 

  3. Sharp, A.J. et al. Nat. Genet. 40, 322–328 (2008).

    Article  CAS  Google Scholar 

  4. International Schizophrenia Consortium. Nature 455, 237–241 (2008).

  5. Stefansson, H. et al. Nature 455, 232–236 (2008).

    Article  CAS  Google Scholar 

  6. Miller, D.T. et al. J. Med. Genet. advance online publication, doi:10.1136/jmg.2008.059907 (19 September 2008).

  7. Neubauer, B.A. et al. Neurology 51, 1608–1612 (1998).

    Article  CAS  Google Scholar 

  8. Elmslie, F.V. et al. Hum. Mol. Genet. 6, 1329–1334 (1997).

    Article  CAS  Google Scholar 

  9. Sander, T. et al. Hum. Mol. Genet. 9, 1465–1472 (2000).

    Article  CAS  Google Scholar 

  10. Helbig, I., Scheffer, I.E., Mulley, J.C. & Berkovic, S.F. Lancet Neurol. 7, 231–245 (2008).

    Article  Google Scholar 

  11. Steinlein, O.K. & Bertrand, D. Biochem. Pharmacol. 76, 1175–1183 (2008).

    Article  CAS  Google Scholar 

  12. Breese, C.R. et al. J. Comp. Neurol. 387, 385–398 (1997).

    Article  CAS  Google Scholar 

  13. Blumenfeld, H. Epilepsia 46 (Suppl. 9), 21–33 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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 (http://ccr.coriell.org/ninds), 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.

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Thomas Sander.

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

Helbig, I., Mefford, H., Sharp, A. et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41, 160–162 (2009). https://doi.org/10.1038/ng.292

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.292

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing