About Us

Epilepsy is one of the most common neurological disorders in humans, with a prevalence of ~1% and a lifetime incidence of up to 3%. Epilepsy is characterized by recurrent seizures due to abnormal, synchronized neuronal firing in the brain. Although it has long been known that epilepsy has a strong genetic component, the epilepsy genes discovered to date explain only a small fraction of disease. In this project, we are working to identify novel genetic causes of the most severe forms of epilepsy, the epileptic encephalopathies. We use state-of-the-art technologies including array comparative genomic hybridization, exome sequencing and targeted candidate gene resequencing to find mutations that cause disease. Using this combination of genomic approaches, we hope to identify new genes and pathways important in brain development and epileptogenesis.

Learn more about this research

Since the introduction of array CGH and SNP microarrays - technologies that allow genome-wide detection of copy number variants (CNVs) - the discovery of novel genomic disorders has increased rapidly. Between 2006-2009, at least 18 novel recurrent disorders have been described. These include rearrangements of 1q21, 15q13, 15q24, 16p13, 17q12 and 17q21. Interestingly, some genomic rearrangements are associated with a wide range of neurocognitive and neuropsychiatric conditions, ranging from mild learning disabilities to epilepsy to schizophrenia. We are interested in understanding the range of phenotypes associated with novel genomic disorders and studying the genetic and epigenetic modifiers that influence clinical outcome.

Learn more about this research

The genomic technologies that our lab uses can be used to identify genetic causes of many different conditions. Our work focuses on congenital anomalies and other pediatric disorders. We have investigated a variety of conditions, including craniosynostosis (premature fusion of the skull bones), congenital diaphragmatic hernia, brain malformations, multiple congenital anomalies, and various prenatally detected birth defects.

Learn more about our research

  • Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Moller RS, Hjalgrim H, Cook J, Geraghty E, O.Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Gazina EV, Suls A, Shendure J, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, Mefford HC^ (2013) GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology (in press)
  • Yu L#, Bennet JT#, Wynn J, Carvill GL, Cheunt Y, Shen Y, Mychaliska G, Azarow K, Crombleholme T, Chung D, Potoka D, Warner B, Bucher B, Stolar C, Aspelund G, Arkovitz M, Mefford HC^, Chung WK^ (2013) Whole Exome Sequencing Identifies de Novo Mutations in GATA6 Associated with Congenital Diaphragmatic Hernia. J Medical Genetics doi: 10.1136/jmedgenet-2013-101989.
  • Mullen SA#, Carvill GL#, Bellows S, Bayly MA, Trucks H, Lal D, Sander T, Berkovic SF, Dibbens LM, Scheffer IE, Mefford HC^ (2013) Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology 81:1507-14.
  • Carvill GL, Regan BM, Yendle SC, O.Roak BJ, Lozovaya N, Bruneau N, Burnashev N, Khan A, Cook J, Sadleir LG, Turner SJ, Tsai MH, Webster R, Ouvrier R, Damiano J, Berkovic SF, Shendure J, Hildebrand M, Szepetowski P, Scheffer IE, Mefford HC^ (2013) GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nature Genetics 45:1073-6. PMCID: PMC3868952.
  • Epi4K Consortium; Epilepsy Phenome/Genome Project, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. (2013) De novo mutation in epileptic encephalopathies. Nature 501:217-21. PMCID: PMC3773011.
  • Carvill GL, Heavin SB, Yendle SC, McMahon JM, O.Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvery S, Malone S, Wallace G, Stanley T, Bye AME, Bleasel A, Howell KB, Kivity S, Mackey MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, MMefford HC^ (2013) TTargeted resequencing in epileptic encephalopathies reveals marked genetic heterogeneity and novel genes including CHD2 and SYNGAP1. Nature Genetics 45:825-30. PMCID: PMC3704157.