High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

FF Hamdan; CT Myers; P Cossette; P Lemay; D Spiegelman; AD Laporte; C Nassif; O Diallo; J Monlong; M Cadieux-Dion; S Dobrzeniecka; C Meloche; K Retterer; MT Cho; JA Rosenfeld; W Bi; C Massicotte; M Miguet; L Brunga; BM Regan; K Mo; C Tam; A Schneider; G Hollingsworth; DR FitzPatrick; A Donaldson; N Canham; E Blair; B Kerr; AE Fry; RH Thomas; J Shelagh; JA Hurst; H Brittain; M Blyth; RR Lebel; EH Gerkes; L Davis-Keppen; Q Stein; WK Chung; SJ Dorison; PJ Benke; E Fassi; N Corsten-Janssen; EJ Kamsteeg; FT Mau-Them; AL Bruel; A Verloes; K Õunap; MH Wojcik; DVF Albert; S Venkateswaran; T Ware; D Jones; YC Liu; SS Mohammad; P Bizargity; CA Bacino; V Leuzzi; S Martinelli; B Dallapiccola; M Tartaglia; L Blumkin; KJ Wierenga; G Purcarin; JJ O'Byrne; S Stockler; A Lehman; B Keren; MC Nougues; C Mignot; S Auvin; C Nava; SM Hiatt; M Bebin; Y Shao; F Scaglia; SR Lalani; RE Frye; IT Jarjour; S Jacques; RM Boucher; E Riou; M Srour; L Carmant; A Lortie; P Major; P Diadori; F Dubeau; G D'Anjou; G Bourque; SF Berkovic; LG Sadleir; PM Campeau; Z Kibar; RG Lafrenière; SL Girard; S Mercimek-Mahmutoglu; C Boelman; GA Rouleau

Journal article

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

FF Hamdan, CT Myers, P Cossette, P Lemay, D Spiegelman, AD Laporte, C Nassif, O Diallo, J Monlong, M Cadieux-Dion, S Dobrzeniecka, C Meloche, K Retterer, MT Cho, JA Rosenfeld, W Bi, C Massicotte, M Miguet, L Brunga, BM Regan Show all

American Journal of Human Genetics | CELL PRESS | Published : 2017

DOI: 10.1016/j.ajhg.2017.09.008

Abstract

Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of indi..

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University of Melbourne Researchers

Amy Schneider Author

Sam Berkovic Author

Ingrid Scheffer Author

Grants

Awarded by National Institute of Child Health and Human Development

Funding Acknowledgements

We thank the individuals participating in this study and their families for their contributions. This study was funded by grants from Genome Canada and Genome Quebec, the Jeanne and Jean-Louis Levesque Foundation (to J.L.M.), the Michael Bahen Chair in Epilepsy Research (to B.A.M.), the Ontario Brain Institute (EpLink), the McLaughlin Foundation and the University of Toronto (to D.M.A. and B.A.M.), and the National Institute of Neurological Disorders and Stroke (RO1 NS069605 to H.C.M.). We thank the members of the massive parallel sequencing and bioinformatics teams at the McGill University and Genome Quebec Innovation Center for their services. S.M.-M. was supported by the University of Toronto McLaughlin Accelerator Grant in Genomic Medicine (MC-2013-08). See Supplemental Data for additional acknowledgements.