title: Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5.
abstract: Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scerri
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Riseley
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia.
authors.forename: Greta
authors.initials: G
authors.lastname: Gillies
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Pope
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Burgess
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Department of Radiology, Royal Children's Hospital Melbourne, Australia ; Department of Radiology, University of Melbourne Melbourne, Australia.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Mandelstam
authors.affiliation: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia Adelaide, Australia ; Sansom Institute for Health Research, University of South Australia Adelaide, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Dibbens
authors.affiliation: Department of Pediatrics, University of Melbourne Melbourne, Australia ; Department of Anatomical Pathology, Royal Children's Hospital Melbourne, Australia.
authors.forename: Chung W
authors.initials: CW
authors.lastname: Chow
authors.affiliation: Department of Neurosurgery, Royal Children's Hospital Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia.
authors.forename: Wirginia
authors.initials: W
authors.lastname: Maixner
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia ; Department of Neurology, Royal Children's Hospital Melbourne, Australia.
authors.forename: Anthony Simon
authors.initials: AS
authors.lastname: Harvey
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia.
authors.forename: Graeme D
authors.initials: GD
authors.lastname: Jackson
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Amor
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia ; Clinical Genetics, Austin Health Melbourne, Australia.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.affiliation: Shriners Hospital Pediatric Research Center, Temple University Philadelphia, Pennsylvania.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Crino
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia.
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.affiliation: The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia ; Department of Neurology, Royal Children's Hospital Melbourne, Australia.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lockhart
authors.affiliation: Department of Pediatrics, University of Melbourne Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia ; Department of Neurology, Royal Children's Hospital Melbourne, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Leventer