PMID- 28223533 OWN - NLM STAT- MEDLINE DCOM- 20180418 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 114 IP - 10 DP - 2017 Mar 7 TI - Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1. PG - 2669-2674 LID - 10.1073/pnas.1614478114 [doi] AB - The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization. FAU - Wielaender, Franziska AU - Wielaender F AD - Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitat Munchen (LMU Munich), D-80539 Munich, Germany. FAU - Sarviaho, Riika AU - Sarviaho R AD - Research Programs Unit, Molecular Neurology, University of Helsinki, 00014 Helsinki, Finland. AD - Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland. AD - Folkhalsan Research Center, 00290 Helsinki, Finland. FAU - James, Fiona AU - James F AD - Department of Clinical Studies, Ontario Veterinary College, University of Guelph, ON, Canada N1G 2W1. FAU - Hytonen, Marjo K AU - Hytonen MK AD - Research Programs Unit, Molecular Neurology, University of Helsinki, 00014 Helsinki, Finland. AD - Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland. AD - Folkhalsan Research Center, 00290 Helsinki, Finland. FAU - Cortez, Miguel A AU - Cortez MA AD - Department of Pediatrics, University of Toronto, Toronto, ON, Canada ON M5S. AD - Neurosciences & Mental Health Program, Peter Gilgan Centre for Research and Learning, SickKids Research Institute, Toronto, ON, Canada M5G 0A4. FAU - Kluger, Gerhard AU - Kluger G AD - Department of Neuropediatrics, Epilepsy Center, Schon Klinik, D-83569 Vogtareuth, Germany. AD - Paracelsus Medical University, 5020 Salzburg, Austria. FAU - Koskinen, Lotta L E AU - Koskinen LL AD - Research Programs Unit, Molecular Neurology, University of Helsinki, 00014 Helsinki, Finland. AD - Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland. AD - Folkhalsan Research Center, 00290 Helsinki, Finland. FAU - Arumilli, Meharji AU - Arumilli M AD - Research Programs Unit, Molecular Neurology, University of Helsinki, 00014 Helsinki, Finland. AD - Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland. AD - Folkhalsan Research Center, 00290 Helsinki, Finland. FAU - Kornberg, Marion AU - Kornberg M AD - Veterinary Hospital Trier, 54294 Trier, Germany. FAU - Bathen-Noethen, Andrea AU - Bathen-Noethen A AD - Veterinary Practice Bathen-Noethen, 51069 Cologne, Germany. FAU - Tipold, Andrea AU - Tipold A AD - Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, 30559 Hannover, Germany. FAU - Rentmeister, Kai AU - Rentmeister K AD - Tierarztliche Praxis fur Neurologie, 97337 Dettelbach, Germany. FAU - Bhatti, Sofie F M AU - Bhatti SF AD - Department of Medicine and Clinical Biology of Small Animals, Ghent University, 9000 Ghent, Belgium. FAU - Hulsmeyer, Velia AU - Hulsmeyer V AD - Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitat Munchen (LMU Munich), D-80539 Munich, Germany. FAU - Boettcher, Irene C AU - Boettcher IC AD - Department of Small Animal Medicine, University of Leipzig, 04103 Leipzig, Germany. FAU - Tastensen, Carina AU - Tastensen C AD - Department of Small Animal Medicine, University of Leipzig, 04103 Leipzig, Germany. FAU - Flegel, Thomas AU - Flegel T AD - Department of Small Animal Medicine, University of Leipzig, 04103 Leipzig, Germany. FAU - Dietschi, Elisabeth AU - Dietschi E AUID- ORCID: 0000-0002-3181-6083 AD - Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland. FAU - Leeb, Tosso AU - Leeb T AD - Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland. FAU - Matiasek, Kaspar AU - Matiasek K AD - Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitat Munchen (LMU Munich) D-80539 Munich, Germany. FAU - Fischer, Andrea AU - Fischer A AD - Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitat Munchen (LMU Munich), D-80539 Munich, Germany; andreafischer@lmu.de hannes.lohi@helsinki.fi. FAU - Lohi, Hannes AU - Lohi H AD - Research Programs Unit, Molecular Neurology, University of Helsinki, 00014 Helsinki, Finland; andreafischer@lmu.de hannes.lohi@helsinki.fi. AD - Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland. AD - Folkhalsan Research Center, 00290 Helsinki, Finland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170221 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Tumor Suppressor Proteins) RN - EC 3.6.1.- (DIRAS1 protein, human) RN - EC 3.6.1.- (GTP Phosphohydrolases) SB - IM MH - Animals MH - Brain/metabolism/physiopathology MH - Disease Models, Animal MH - Dogs MH - Epilepsies, Myoclonic/*genetics/pathology MH - GTP Phosphohydrolases/*genetics MH - *Gene Deletion MH - Humans MH - Photosensitivity Disorders/*genetics/pathology MH - Tumor Suppressor Proteins/*genetics PMC - PMC5347561 OTO - NOTNLM OT - Ras OT - canine OT - juvenile OT - photosensitivity OT - seizure COIS- Conflict of interest statement: H.L. is one of the owners of the Genoscoper Ltd., which provides the gene test developed based on the study. EDAT- 2017/02/23 06:00 MHDA- 2018/04/19 06:00 PMCR- 2017/02/21 CRDT- 2017/02/23 06:00 PHST- 2017/02/23 06:00 [pubmed] PHST- 2018/04/19 06:00 [medline] PHST- 2017/02/23 06:00 [entrez] PHST- 2017/02/21 00:00 [pmc-release] AID - 1614478114 [pii] AID - 201614478 [pii] AID - 10.1073/pnas.1614478114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2669-2674. doi: 10.1073/pnas.1614478114. Epub 2017 Feb 21.