De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy

SF Berkovic; B Grinton; T Dixon-Salazar; BL Laughlin; L Lubbers; J Milder; DB Goldstein; EL Heinzen; L Bier; ME Ernst; NC Lippa; MS Mulhern; TM Afgani; V Aggarwal; N Stong; DH Lowenstein; S Cornes; K Johnson; R Stewart; V Whittemore; K Angione; S Demarest; M Gibbons; C Joshi; K Park; CW Bazil; H Choi; J Bluvstein; O Devinsky; P Dugan; P Tolete; E Brimble; C Campbell; C Chambers; H Goodkin; L Jansen; MR Cilio; A Numis; N Singhal; J Sullivan; M Ciliberto; N Delanty; D Dlugos; H Dubbs; I Helbig; E Marsh; A Martinez; W Gallentine; MA Makati; J Millichap; Y Moskovich; J Millichap; A Poduri; B Sheidley; L Smith; A Taylor; B Porter; TT Sands; JJ Riviello; IE Scheffer; AS Allen; R Hamid; KL Helbig; S Tang; MH Meisler; S Petrovski; J Pfotenhauer

Journal article

De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy

SF Berkovic, B Grinton, T Dixon-Salazar, BL Laughlin, L Lubbers, J Milder, DB Goldstein, EL Heinzen, L Bier, ME Ernst, NC Lippa, MS Mulhern, TM Afgani, V Aggarwal, N Stong, DH Lowenstein, S Cornes, K Johnson, R Stewart, V Whittemore Show all

Genetics in Medicine | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/gim.2017.100

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Abstract

Purpose: As part of the Epilepsy Genetics Initiative, we reevaluated clinically generated exome sequence data from 54 epilepsy patients and their unaffected parents to identify molecular diagnoses not provided in the initial diagnostic interpretation. Methods: We compiled and analyzed exome sequence data from 54 genetically undiagnosed trios using a validated analysis pipeline. We evaluated the significance of the genetic findings by reanalyzing sequence data generated at Ambry Genetics, and from a number of additional case and control cohorts. Results: In 54 previously undiagnosed trios, we identified two de novo missense variants in SCN8A in the highly expressed alternative exon 5 A-An exo..

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University of Melbourne Researchers

Sam Berkovic Author

Bronwyn Grinton Author

Ingrid Scheffer Author

Slave Petrovski Author

Related Projects (1)

3 of 7 Epi4K: Gene discovery in 4,000 epilepsy genomes

DESCRIPTION (provided by applicant): The primary goal of the Epi4K Center Without Walls is to increase understanding of the genetic basis of..

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Awarded by National Institute of Neurological Disorders and Stroke

Funding Acknowledgements

The authors acknowledge Citizens United for Research in Epilepsy (339143) and the National Institute for Neurological Disorders and Stroke (U01-NS077303-04S1) for providing the funding to make this research possible. We thank the patients and families enrolled in the EGI for their participation in this research and dedication to furthering our understanding of the genetic causes of epilepsy. We also thank the external providers and clinicians who referred their patients and provided phenotype data.