PMID- 26000329 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150522 LR - 20220317 IS - 2328-9503 (Print) IS - 2328-9503 (Electronic) IS - 2328-9503 (Linking) VI - 2 IP - 5 DP - 2015 May TI - Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. PG - 575-80 LID - 10.1002/acn3.191 [doi] AB - 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. FAU - Scerri, Thomas AU - Scerri T AD - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia. FAU - Riseley, Jessica R AU - Riseley JR AD - Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia. FAU - Gillies, Greta AU - Gillies G AD - Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia. FAU - Pope, Kate AU - Pope K AD - Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia. FAU - Burgess, Rosemary AU - Burgess R AD - The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia. FAU - Mandelstam, Simone A AU - Mandelstam SA AD - 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. FAU - Dibbens, Leanne AU - Dibbens L AD - 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. FAU - Chow, Chung W AU - Chow CW AD - Department of Pediatrics, University of Melbourne Melbourne, Australia ; Department of Anatomical Pathology, Royal Children's Hospital Melbourne, Australia. FAU - Maixner, Wirginia AU - Maixner W AD - Department of Neurosurgery, Royal Children's Hospital Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia. FAU - Harvey, Anthony Simon AU - Harvey AS AD - 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. FAU - Jackson, Graeme D AU - Jackson GD AD - The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia. FAU - Amor, David J AU - Amor DJ AD - Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia. FAU - Delatycki, Martin B AU - Delatycki MB AD - 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. FAU - Crino, Peter B AU - Crino PB AD - Shriners Hospital Pediatric Research Center, Temple University Philadelphia, Pennsylvania. FAU - Berkovic, Samuel F AU - Berkovic SF AD - The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia. FAU - Scheffer, Ingrid E AU - Scheffer IE AD - 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. FAU - Bahlo, Melanie AU - Bahlo M AD - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia. FAU - Lockhart, Paul J AU - Lockhart PJ AD - Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia. FAU - Leventer, Richard J AU - Leventer RJ AD - Department of Pediatrics, University of Melbourne Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia ; Department of Neurology, Royal Children's Hospital Melbourne, Australia. LA - eng GR - R01 NS082343/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20150312 PL - United States TA - Ann Clin Transl Neurol JT - Annals of clinical and translational neurology JID - 101623278 PMC - PMC4435711 EDAT- 2015/05/23 06:00 MHDA- 2015/05/23 06:01 PMCR- 2015/03/12 CRDT- 2015/05/23 06:00 PHST- 2015/02/09 00:00 [received] PHST- 2015/02/09 00:00 [accepted] PHST- 2015/05/23 06:00 [entrez] PHST- 2015/05/23 06:00 [pubmed] PHST- 2015/05/23 06:01 [medline] PHST- 2015/03/12 00:00 [pmc-release] AID - 10.1002/acn3.191 [doi] PST - ppublish SO - Ann Clin Transl Neurol. 2015 May;2(5):575-80. doi: 10.1002/acn3.191. Epub 2015 Mar 12.