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

16p11.2 European Consortium, EPICURE Consortium, The EuroEPINOMICS Consortium, Rikke Steensbjerre Møller (Member of author group)

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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 × 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 × 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.

Original languageEnglish
JournalHuman Molecular Genetics
Volume23
Issue number22
Pages (from-to)6069-80
ISSN0964-6906
DOIs
Publication statusPublished - 15. Nov 2014

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Keywords

  • Child
  • Child, Preschool
  • Chromosome Duplication
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 15
  • Chromosomes, Human, Pair 16
  • Chromosomes, Human, Pair 22
  • DNA Copy Number Variations
  • Epilepsy, Rolandic
  • Female
  • Humans
  • Infant
  • Male
  • Polymorphism, Single Nucleotide

Cite this

16p11.2 European Consortium, EPICURE Consortium, The EuroEPINOMICS Consortium, & Møller, R. S. (2014). 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Human Molecular Genetics, 23(22), 6069-80. https://doi.org/10.1093/hmg/ddu306