Please use this identifier to cite or link to this item:
Title: Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy.
Austin Authors: Ricos, Michael G;Hodgson, Bree L;Pippucci, Tommaso;Saidin, Akzam;Ong, Yeh Sze;Heron, Sarah E;Licchetta, Laura;Bisulli, Francesca;Bayly, Marta A;Hughes, James;Baldassari, Sara;Palombo, Flavia;Santucci, Margherita;Meletti, Stefano;Berkovic, Samuel F ;Rubboli, Guido;Thomas, Paul Q;Scheffer, Ingrid E ;Tinuper, Paolo;Geoghegan, Joel;Schreiber, Andreas W;Dibbens, Leanne M
Affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia
Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia
Molecular Neurogenomics Research Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia
Novocraft Technologies Sdn Bhd, Selangor, Malaysia
School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia
Medical Genetics Unit, Polyclinic Sant'Orsola-Malpighi University Hospital, Bologna, Italy
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, AUSL Modena, Modena, Italy
Danish Epilepsy Center, Filadelfia/University of Copenhagen, Dianalund, Denmark
IRCCS Institute of Neurological Sciences, Neurology Unit, Bellaria Hospital, Bologna, Italy
Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
Issue Date: Jan-2016 2015-12-12
Publication information: Annals of neurology 2016; 79(1): 120-31
Abstract: Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy. We used targeted capture and next-generation sequencing to analyze 404 unrelated probands with focal epilepsy. We performed exome sequencing on two families with multiple members affected with focal epilepsy and linkage analysis on one of these. In our cohort of 404 unrelated focal epilepsy patients, we identified five mutations in NPRL2 and five in NPRL3. Exome sequencing analysis of two families with focal epilepsy identified NPRL2 and NPRL3 as the top candidate-causative genes. Some patients had focal epilepsy associated with brain malformations. We also identified 18 new mutations in DEPDC5. We have identified NPRL2 and NPRL3 as two new focal epilepsy genes that also play a role in the mTOR-signaling pathway. Our findings show that mutations in GATOR1 complex genes are the most significant cause of familial focal epilepsy identified to date, including cases with brain malformations. It is possible that deregulation of cellular growth control plays a more important role in epilepsy than is currently recognized.
DOI: 10.1002/ana.24547
ORCID: 0000-0002-2311-2174
PubMed URL: 26505888
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Dec 2, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.