Somatic Mutations in Surgical Epilepsy Tissue

Project Details

Somatic mutagenesis, occurring post-fertilization, may play an important role in causation of the severe end of the focal epilepsy spectrum. To unravel this contribution, we are studying two privileged resources. First, a unique set of 50 patients with focal epilepsy refractory to anti-epileptic drugs who have had epilepsy surgery, facilitate an exciting new approach to this problem. Second, we are taking advantage of our large biobank of 150 formalin-fixed paraffin-embedded (FFPE) brain specimens resected from patients with focal epilepsy over the last 10 years. We are applying molecular inversion probe (MIP) gene capture panel (Figure 4) and exome sequencing (for DNA), and RNA sequencing, respectively, which are well established techniques for deep sequencing fresh-frozen tissue in our hands.

De novo mutation in the KCNT1 potassium channel gene identified by MIP capture and sequencing using our focal epilepsy gene panel (left). The mutation is located in the cytoplasmic domain of the channel protein (right). Adapted from Hildebrand et al 2016 Neurology.


  • Dr Michael Hildebrand BBiomed Sci, BSc (Hons), PhD - Laboratory Head
  • John Damiano BSc (Hons) - Senior Research Assistant
  • Matthew Coleman BSc (Hons) - Research Assistant
  • Joshua Reid BSc - Technical Assistant
  • Zimeng (Daisy) Ye - PhD student
  • Tim Green BSc - Honours student


  • Associate Professor Angela Morgan, Murdoch Children's Research Institute
  • Professor Melanie Bahlo, Walter and Eliza Hall Institute
  • Professor Patrick Kwan, Royal Melbourne Hospital
  • Associate Professor Heather Mefford, University of Washington


  1. National Health and Medical Research Council (NHMRC) Project Grant APP1129054 2017-2020, Detection of Somatic Mutations in Sporadic Epilepsies, Epilepsy Research Centre, University of Melbourne, Australia ($1,256,165 AUD) CIA: Prof. Samuel F Berkovic, CIB: Dr. Michael S Hildebrand, CIC: Dr. Slave Petrovski, CID: Dr. Snezana Maljevic
  2. National Health and Medical Research Council (NHMRC) Project Grant APP1079058 2015-2017, Exploring somatic mutation in focal epilepsies, Epilepsy Research Centre and Royal Melbourne Hospital, University of Melbourne, Australia, and University of Washington, Seattle, USA ($684,492 AUD) CIA: Dr. Michael S Hildebrand, CIB: A/Prof. Heather C. Mefford, CIC: Prof. Patrick Kwan

Research Publications

  1. Hildebrand MS, Griffin NG, Damiano JA, Cops EJ, Burgess R, Ozturk E, Jones NC, Leventer RJ, Freeman JL, Harvey AS, Sadleir LG, Scheffer IE, Major H, Darbro BW, Allen AS, Goldstein DB, Kerrigan JF, Berkovic SF, Heinzen EL. Mutations of the Sonic Hedgehog Pathway Underlie Hypothalamic Hamartoma with Gelastic Epilepsy. Am J Hum Genet. 2016 Aug 4;99(2):423-9.
  2. Hildebrand MS, Myers CT, Carvill GL, Regan BM, Damiano JA, Mullen SA, Newton MR, Nair U, Gazina EV, Milligan CJ, Reid CA, Petrou S, Scheffer IE, Berkovic SF, Mefford HC. A targeted resequencing gene panel for focal epilepsy. Neurology. 2016 Apr 26;86(17):1605-12.

Research Group

Translational Neurogenetics Laboratory

Key Contact

For further information about this research, please contact the research group leader.

Department / Centre


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