Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 (original) (raw)

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Acknowledgements

We thank the individuals with epileptic encephalopathies and their families for participating in our research. H.C.M. is supported by a grant from the US National Institutes of Health (NIH; National Institute of Neurological Disorders and Stroke (NINDS) 1R01NS069605) and is a recipient of a Burroughs Wellcome Fund Career Award for Medical Scientists. This work was supported by the National Health and Medical Research Council of Australia (program grant 628952 to S.F.B. and I.E.S., practitioner fellowship 1006110 to I.E.S.) and a Health Research Council of New Zealand project grant to L.G.S.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA
    Gemma L Carvill, Joseph Cook, Adiba Khan & Heather C Mefford
  2. Department of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
    Sinéad B Heavin, Simone C Yendle, Jacinta M McMahon, Samuel F Berkovic & Ingrid E Scheffer
  3. Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    Brian J O'Roak & Jay Shendure
  4. Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, Washington, USA
    Michael O Dorschner & Molly Weaver
  5. Veteran Affairs Puget Sound Health Care System, Seattle, Washington, USA
    Michael O Dorschner & Molly Weaver
  6. Neurosciences Children's Health Queensland, Royal and Mater Children's Hospitals, Brisbane, Queensland, Australia
    Sophie Calvert, Stephen Malone & Geoffrey Wallace
  7. Department of Paediatrics, School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
    Thorsten Stanley & Lynette G Sadleir
  8. Department of Paediatric Neurology, University of New South Wales, Sydney Children's Hospital, Sydney, New South Wales, Australia
    Ann M E Bye
  9. Department of Neurology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
    Andrew Bleasel
  10. Department of Neurology, The Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia
    Katherine B Howell, Mark T Mackay, Jeremy L Freeman & Ingrid E Scheffer
  11. Epilepsy Unit, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel
    Sara Kivity
  12. Critical Care & Neurosciences Theme, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
    Mark T Mackay & Jeremy L Freeman
  13. Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital, Melbourne, Victoria, Australia
    Mark T Mackay & Ingrid E Scheffer
  14. Paediatric Neurology, Monash Medical Centre, Melbourne, Victoria, Australia
    Victoria Rodriguez-Casero
  15. TY Nelson Department of Neurology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
    Richard Webster & Deepak Gill
  16. Department of Neurology, Tel-Aviv University, Tel-Aviv, Israel
    Amos Korczyn
  17. Tel-Aviv University Medical School, Tel-Aviv, Israel
    Zaid Afawi
  18. Department of Pediatrics, Carmel Medical Center, Technion Faculty of Medicine, Haifa, Israel
    Nathanel Zelnick
  19. Metabolic-Neurogenetic Service, Wolfson Medical Center, Holon, Israel
    Tally Lerman-Sagie & Dorit Lev
  20. Danish Epilepsy Centre, Dianalund, Denmark
    Tally Lerman-Sagie & Rikke S Møller
  21. Department of Medicine, Division of Neurology, University of Toronto, Toronto Western Hospital, Krembil Neurosciences Program, Toronto, Ontario, Canada
    Danielle M Andrade
  22. Florey Institute, Melbourne, Victoria, Australia
    Ingrid E Scheffer

Authors

  1. Gemma L Carvill
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  2. Sinéad B Heavin
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  3. Simone C Yendle
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  4. Jacinta M McMahon
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  5. Brian J O'Roak
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  6. Joseph Cook
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  7. Adiba Khan
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  8. Michael O Dorschner
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  9. Molly Weaver
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  10. Sophie Calvert
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  11. Stephen Malone
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  12. Geoffrey Wallace
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  13. Thorsten Stanley
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  14. Ann M E Bye
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  15. Andrew Bleasel
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  16. Katherine B Howell
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  17. Sara Kivity
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  18. Mark T Mackay
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  19. Victoria Rodriguez-Casero
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  20. Richard Webster
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  21. Amos Korczyn
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  22. Zaid Afawi
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  23. Nathanel Zelnick
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  24. Tally Lerman-Sagie
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  25. Dorit Lev
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  26. Rikke S Møller
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  27. Deepak Gill
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  28. Danielle M Andrade
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  29. Jeremy L Freeman
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  30. Lynette G Sadleir
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  31. Jay Shendure
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  32. Samuel F Berkovic
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  33. Ingrid E Scheffer
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  34. Heather C Mefford
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Contributions

G.L.C., H.C.M. and I.E.S. designed the study and wrote the manuscript. H.C.M. and I.E.S. supervised the study. G.L.C. constructed libraries, developed the variant calling pipeline (with assistance from J.C.) and analyzed the sequence data. B.J.O. and J.S. developed the molecular inversion probe (MIP) methodology and analysis pipeline. S.B.H., S.C.Y., J.M.M., S.C., S.M., G.W., T.S., A.M.E.B., A.B., K.B.H., S.K., M.T.M., V.R.-C., R.W., A. Korczyn, Z.A., N.Z., T.L.-S., D.L., R.S.M., D.G., D.M.A., J.L.F., L.G.S., S.F.B. and I.E.S. performed phenotypic analysis. S.B.H., J.M.M., S.F.B. and I.E.S. critically reviewed the manuscript. G.L.C. and A. Khan performed segregation analysis experiments. M.O.D. and M.W. performed Illumina HiSeq sequencing.

Corresponding authors

Correspondence toIngrid E Scheffer or Heather C Mefford.

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The authors declare no competing financial interests.

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Carvill, G., Heavin, S., Yendle, S. et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.Nat Genet 45, 825–830 (2013). https://doi.org/10.1038/ng.2646

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