Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures

Nature Genetics
R H WallaceS F Berkovic

Abstract

Epilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants. We have found a mutation in a gene encoding a GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a recognized genetic relationship between FS and CAE, yet the two syndromes have different ages of onset, and the physiology of absences and convulsions is distinct. This suggests the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.

References

Nov 1, 1993·Annals of Neurology·A R Brooks-Kayal, D B Pritchett
Jul 1, 1994·Human Heredity·A A SchäfferR W Cottingham
Oct 29, 1993·Science·M SteriadeT J Sejnowski
Apr 1, 1997·Epilepsia·R W Olsen, M Avoli
Mar 1, 1997·Brain : a Journal of Neurology·I E Scheffer, S F Berkovic
Feb 7, 1998·Science·C BiervertO K Steinlein
Jan 22, 2000·Epilepsia·F U Knudsen
Dec 6, 2000·Current Opinion in Pediatrics·I E Scheffer, S F Berkovic

❮ Previous
Next ❯

Citations

Jan 24, 2007·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Melodie R WinawerAbraham A Palmer
Mar 31, 2010·Pflügers Archiv : European journal of physiology·Aristea S Galanopoulou
Aug 24, 2011·Pflügers Archiv : European journal of physiology·Nathalie LerescheVincenzo Crunelli
Jul 10, 2007·Current Neurology and Neuroscience Reports·David A Greenberg, Deb K Pal
Jun 27, 2013·Current Pain and Headache Reports·P R BauerG H Visser
Sep 14, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Gholam K MotamediStefano Vicini
Nov 2, 2004·Nature Cell Biology·Thomas J JentschJens C Fuhrmann
Dec 8, 2009·Nature Medicine·David W CopeVincenzo Crunelli
Apr 22, 2004·Nature Reviews. Neuroscience·Ortrud K Steinlein
Jun 23, 2004·Nature Reviews. Neuroscience·Michael A Rogawski, Wolfgang Löscher
Apr 3, 2008·Nature Reviews. Neuroscience·Tija C JacobRachel Jurd
May 4, 2002·Nature Reviews. Neuroscience·Vincenzo Crunelli, Nathalie Leresche
Feb 1, 2007·European Journal of Human Genetics : EJHG·Kate V EverettMark Gardiner
Mar 13, 2002·Epilepsia·S F Berkovic, I E Scheffer
Aug 17, 2004·Epilepsy Currents·C Guin-Ting Wong, O Carter Snead
Aug 17, 2004·Epilepsy Currents·Jeffrey L. Noebels
Sep 26, 2003·The New England Journal of Medicine·Bernard S Chang, Daniel H Lowenstein
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·John C OakleyWilliam A Catterall
May 9, 2009·Journal of Neurotrauma·Sinziana AvramescuIgor Timofeev
Feb 1, 2006·Brain : a Journal of Neurology·Céline DubéTallie Z Baram
Jul 7, 2007·Cerebral Cortex·Marco FediDavid C Reutens
Jan 17, 2009·Human Molecular Genetics·Toshimitsu SuzukiKazuhiro Yamakawa
Nov 24, 2005·Epilepsia·Mark Gardiner
Nov 24, 2005·Epilepsia·Hal Blumenfeld
Dec 20, 2005·Epilepsia·Ruth Ottman
Dec 20, 2005·Epilepsia·Ingrid E SchefferSamuel F Berkovic
Oct 24, 2006·Epilepsia·Sara Shostak, Ruth Ottman
Jun 16, 2007·Epilepsia·Giuliano AvanziniMassimo Mantegazza
Feb 26, 2008·Epilepsia·Heneu O TanSteven Petrou
Jan 27, 2010·Epilepsia·Ruth OttmanIngrid E Scheffer
Sep 14, 2010·Epilepsia·Andrew Escayg, Alan L Goldin
Sep 8, 2005·Epilepsy Currents·Andre Lagrange
Jan 30, 2007·Epilepsy Currents·Richard W Olsen
Apr 28, 2009·Epilepsy Currents·Robert L Macdonald, Jing-Qiong Kang
Nov 25, 2004·Epilepsy Currents·Alfred L George
Jun 15, 2007·Genes, Brain, and Behavior·L M DibbensJ C Mulley
Jan 28, 2009·Genes, Brain, and Behavior·S TokudaW N Frankel
Dec 18, 2002·Journal of Neurology, Neurosurgery, and Psychiatry·J O WilloughbyR A Wilcox
Jan 11, 2005·Postgraduate Medical Journal·T D Graves, M G Hanna

❮ Previous
Next ❯

Related Concepts

Related Feeds

Absence Epilepsy

Absence epilepsy is a common seizure disorder in children which can produce chronic psychosocial sequelae. Discover the latest research on absence epilepsies here.