16p11.2 600 kb duplications confer risk for typical and atypical Rolandic epilepsy

Item Type:	Article
Title:	16p11.2 600 kb duplications confer risk for typical and atypical Rolandic epilepsy
Creators Name:	Reinthaler, E.M. and Lal, D. and Lebon, S. and Hildebrand, M.S. and Dahl, H.H.M. and Regan, B.M. and Feucht, M. and Steinboeck, H. and Neophytou, B. and Ronen, G.M. and Roche, L. and Gruber-Sedlmayr, U. and Geldner, J. and Haberlandt, E. and Hoffmann, P. and Herms, S. and Gieger, C. and Waldenberger, M. and Franke, A. and Wittig, M. and Schoch, S. and Becker, A.J. and Hahn, A. and Maennik, K. and Toliat, M.R. and Winterer, G. and Lerche, H. and Nuernberg, P. and Mefford, H. and Scheffer, I.E. and Berkovic, S.F. and Beckmann, J.S. and Sander, T. and Jacquemont, S. and Reymond, A. and Zimprich, F. and Neubauer, B.A.
Abstract:	Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 x 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 x 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.
Keywords:	Chromosome Duplication, DNA Copy Number Variations, Pair 1 Human Chromosomes, Pair 15 Human Chromosomes, Pair 16 Human Chromosomes, Pair 22 Human Chromosomes, Rolandic Epilepsy, Single Nucleotide Polymorphism
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	23
Number:	22
Page Range:	6069-6080
Date:	15 November 2014
Official Publication:	https://doi.org/10.1093/hmg/ddu306
PubMed:	View item in PubMed

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