Journal article

Rare copy number variants are an important cause of epileptic encephalopathies

Heather C Mefford, Simone C Yendle, Cynthia Hsu, Joseph Cook, Eileen Geraghty, Jacinta M McMahon, Orvar Eeg-Olofsson, Lynette G Sadleir, Deepak Gill, Bruria Ben-Zeev, Tally Lerman-Sagie, Mark Mackay, Jeremy L Freeman, Eva Andermann, James T Pelakanos, Ian Andrews, Geoffrey Wallace, Evan E Eichler, Samuel F Berkovic, Ingrid E Scheffer

ANNALS OF NEUROLOGY | WILEY | Published : 2011

Abstract

OBJECTIVE: Rare copy number variants (CNVs)--deletions and duplications--have recently been established as important risk factors for both generalized and focal epilepsies. A systematic assessment of the role of CNVs in epileptic encephalopathies, the most devastating and often etiologically obscure group of epilepsies, has not been performed. METHODS: We evaluated 315 patients with epileptic encephalopathies characterized by epilepsy and progressive cognitive impairment for rare CNVs using a high-density, exon-focused, whole-genome oligonucleotide array. RESULTS: We found that 25 of 315 (7.9%) of our patients carried rare CNVs that may contribute to their phenotype, with at least one-half b..

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Awarded by NIH


Awarded by Burroughs Wellcome Fund


Awarded by National Health and Medical Research Council of Australia


Awarded by NIH/NINDS


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

This research was supported by the NIH (NINDS 1R01NS069605 to H. C. M.); Career Award for Medical Scientists from the Burroughs Wellcome Fund (to H. C. M.); and the National Health and Medical Research Council of Australia (400121 to S. F. B. and I. E. S.). E. E. E is an investigator of Howard Hughes Medical Institute.E.A. has grants/grants pending and received payments for lectures from UCB Pharma Clinical Trials in Epilepsy. B.B.-Z. is employed as the head of a pediatric neurology unit and has grants/grants pending from GIF for other studies. S. B. has received grant(s) from the National Health and Medical Research Council; has received honoraria from UCB; has a patent for PCDH19 testing planned; has received payment for development of educational presentations from UCB Pharma, Novartis Pharmaceuticals, Sanofi-Aventis, and Jansen Cilag; has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies, with no financial return; was a consultant to Bionomics and Athena diagnostics over 3 years ago. J.C. and E. G. received grants from the NIH. E. E. E. received a grant from the Howard Hughes Medical Institute; is a consultant for and a member of the Scientific Advisory Board of Pacific Biosystems; is on the board of the Simons Foundation Autism Research Initiative (SFARI) Structural Variation Project, Yerkes National Primate Center, and International Cancer Genome Consortium, Ontario Institute of Cancer Research; has received various payments for lectures including service on speakers bureaus; Payment for development of the educational presentations (Henry Stewart Talks); and has stock/stock options for Pacific Biosystems. J. M. and S.Y. have received grants from the National Health and Medical Research Council of Australia. H. M. has received a grant from the NIH/NINDS (1R01NS069605); received support for travel to meetings for the study or other purposes from Sanger Center (Invited speaker, Genomic Disorders 2011 - The Genomics of Rare Diseases) and NIH/NINDS (Invited participant, Genetics of Epilepsy Workshop); and was a consultant for the Simons Foundation (SFARI Gene Advisory Board). L. S. has received grants from the Health and Research Council of New Zealand and Cure Kids (Child Health Research Foundation); and received support for travel to meetings for the study or other purposes from the International League Against Epilepsy (ILAE classification task force). I. S. was on the Asian Oceanian Board of Janssen-Cilag; received payment for lectures including service on speakers bureaus from UCB, Janssen-Cilag, Athena Diagnostics, and Eli-Lilly; has a patent pending WO61/010176, Therapeutic Compound (filed 2008); has received payment for development of educational presentations for Athena Diagnostics; has received travel/accommodations/meeting expenses unrelated to activities listed from UCB, Biocodex, and Athena Diagnostics.