Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5.

Autor: Scerri T; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia., Riseley JR; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia., Gillies G; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia., Pope K; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia., Burgess R; The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia., Mandelstam SA; 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., Dibbens L; 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., Chow CW; Department of Pediatrics, University of Melbourne Melbourne, Australia ; Department of Anatomical Pathology, Royal Children's Hospital Melbourne, Australia., Maixner W; Department of Neurosurgery, Royal Children's Hospital Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia., Harvey AS; 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., Jackson GD; The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia., Amor DJ; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia., Delatycki MB; 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., Crino PB; Shriners Hospital Pediatric Research Center, Temple University Philadelphia, Pennsylvania., Berkovic SF; The Florey Institute of Neuroscience and Mental Health Melbourne, Australia ; Epilepsy Research Centre, University of Melbourne, Austin Health Melbourne, Australia., Scheffer IE; 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., Bahlo M; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, Parkville, Victoria, Australia., Lockhart PJ; Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute Parkville, Victoria, Australia ; Department of Pediatrics, University of Melbourne Melbourne, Australia., Leventer RJ; Department of Pediatrics, University of Melbourne Melbourne, Australia ; Murdoch Childrens Research Institute Melbourne, Australia ; Department of Neurology, Royal Children's Hospital Melbourne, Australia.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2015 May; Vol. 2 (5), pp. 575-80. Date of Electronic Publication: 2015 Mar 12.
DOI: 10.1002/acn3.191
Abstrakt: 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.
Databáze: MEDLINE
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