Address correspondence to Dr Zimprich, Department of Neurology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria. E-mail: [email protected]Search for more papers by this author

Eva M. Reinthaler PhD,

Eva M. Reinthaler PhD

Department of Neurology, Medical University of Vienna, Vienna, Austria

Search for more papers by this author

Borislav Dejanovic PhD,

Borislav Dejanovic PhD

Institute of Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany

Search for more papers by this author

Dennis Lal PhD,

Dennis Lal PhD

Department of Neuropediatrics, University Medical Center Giessen and Marburg, Giessen, Germany

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

Marcus Semtner PhD,

Marcus Semtner PhD

RNA Editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Search for more papers by this author

Yvonne Merkler MSc,

Yvonne Merkler MSc

Institute of Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany

Search for more papers by this author

Annika Reinhold,

Annika Reinhold

RNA Editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Search for more papers by this author

Dorothea A. Pittrich BSc,

Dorothea A. Pittrich BSc

Department of Neurology, Medical University of Vienna, Vienna, Austria

Search for more papers by this author

Christoph Hotzy BSc,

Christoph Hotzy BSc

Department of Neurology, Medical University of Vienna, Vienna, Austria

Search for more papers by this author

Martha Feucht MD,

Martha Feucht MD

Department of Pediatrics, Medical University of Vienna, Vienna, Austria

Search for more papers by this author

Hannelore Steinböck MD,

Hannelore Steinböck MD

Private Practice of Pediatrics, Vienna, Austria

Search for more papers by this author

Ursula Gruber-Sedlmayr MD,

Ursula Gruber-Sedlmayr MD

Department of Pediatrics, Medical University of Graz, Graz, Austria

Search for more papers by this author

Gabriel M. Ronen MD,

Gabriel M. Ronen MD

Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada

Search for more papers by this author

Birgit Neophytou MD,

Birgit Neophytou MD

Department of Neuropediatrics, St Anna Children's Hospital, Vienna, Austria

Search for more papers by this author

Julia Geldner MD,

Julia Geldner MD

Department of Pediatrics, SMZ Süd - Kaiser-Franz-Josef-Hospital, Vienna, Austria

Search for more papers by this author

Edda Haberlandt MD,

Edda Haberlandt MD

Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria

Search for more papers by this author

Hiltrud Muhle MD,

Hiltrud Muhle MD

Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian Albrechts University, Kiel, Germany

Search for more papers by this author

M. Arfan Ikram MD, PhD,

M. Arfan Ikram MD, PhD

Departments of Epidemiology, Neurology, and Radiology, Erasmus Medical Center, Rotterdam, the Netherlands

Search for more papers by this author

Cornelia M. van Duijn PhD,

Cornelia M. van Duijn PhD

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

Search for more papers by this author

Andre G. Uitterlinden PhD,

Andre G. Uitterlinden PhD

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands

Search for more papers by this author

Albert Hofman MD, PhD,

Albert Hofman MD, PhD

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

Search for more papers by this author

Janine Altmüller MD,

Janine Altmüller MD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Institute of Human Genetics, University of Cologne, Cologne, Germany

Search for more papers by this author

Amit Kawalia MSc,

Amit Kawalia MSc

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

Mohammad R. Toliat PhD,

Mohammad R. Toliat PhD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

EuroEPINOMICS Consortium,

EuroEPINOMICS Consortium

Search for more papers by this author

Peter Nürnberg PhD,

Peter Nürnberg PhD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

Search for more papers by this author

Holger Lerche MD,

Holger Lerche MD

Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany

Search for more papers by this author

Michael Nothnagel PhD,

Michael Nothnagel PhD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

Holger Thiele MD,

Holger Thiele MD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

Thomas Sander MD,

Thomas Sander MD

Cologne Center for Genomics, University of Cologne, Cologne, Germany

Search for more papers by this author

Jochen C. Meier PhD,

Jochen C. Meier PhD

RNA Editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Braunschweig University of Technology, Zoological Institute, Division of Cell Physiology, Braunschweig, Germany

Search for more papers by this author

Günter Schwarz PhD,

Günter Schwarz PhD

Institute of Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

Search for more papers by this author

Bernd A. Neubauer MD,

Bernd A. Neubauer MD

Department of Neuropediatrics, University Medical Center Giessen and Marburg, Giessen, Germany

Search for more papers by this author

Fritz Zimprich MD, PhD,

Corresponding Author

Fritz Zimprich MD, PhD

Department of Neurology, Medical University of Vienna, Vienna, Austria

First published: 27 February 2015

https://doi.org/10.1002/ana.24395

Citations: 56

Members of the EuroEPINOMICS Consortium are listed in the Appendix on page 985.

Share a link

Email
Wechat
Bluesky

Abstract

Objective

To test whether mutations in γ-aminobutyric acid type A receptor (GABA_A-R) subunit genes contribute to the etiology of rolandic epilepsy (RE) or its atypical variants (ARE).

Methods

We performed exome sequencing to compare the frequency of variants in 18 GABA_A-R genes in 204 European patients with RE/ARE versus 728 platform-matched controls. Identified GABRG2 variants were functionally assessed for protein stability, trafficking, postsynaptic clustering, and receptor function.

Results

Of 18 screened GABA_A-R genes, we detected an enrichment of rare variants in the GABRG2 gene in RE/ARE patients (5 of 204, 2.45%) in comparison to controls (1 of 723, 0.14%; odds ratio = 18.07, 95% confidence interval = 2.01–855.07, p = 0.0024, p_corr = 0.043). We identified a GABRG2 splice variant (c.549-3T>G) in 2 unrelated patients as well as 3 nonsynonymous variations in this gene (p.G257R, p.R323Q, p.I389V). Functional assessment showed reduced surface expression of p.G257R and decreased GABA-evoked currents for p.R323Q. The p.G257R mutation displayed diminished levels of palmitoylation, a post-translational modification crucial for trafficking of proteins to the cell membrane. Enzymatically raised palmitoylation levels restored the surface expression of the p.G257R variant γ2 subunit.

Interpretation

The statistical association and the functional evidence suggest that mutations of the GABRG2 gene may increase the risk of RE/ARE. Restoring the impaired membrane trafficking of some GABRG2 mutations by enhancing palmitoylation might be an interesting therapeutic approach to reverse the pathogenic effect of such mutants. Ann Neurol 2015;77:972–986

Supporting Information

References

1Gobbi G, Boni A, Filippini M. The spectrum of idiopathic Rolandic epilepsy syndromes and idiopathic occipital epilepsies: from the benign to the disabling. Epilepsia 2006; 47(suppl 2): 62–66.
10.1111/j.1528-1167.2006.00693.x
PubMed Web of Science® Google Scholar
2Guerrini R, Pellacani S. Benign childhood focal epilepsies. Epilepsia 2012; 53(suppl 4): 9–18.
10.1111/j.1528-1167.2012.03609.x
PubMed Web of Science® Google Scholar
3Fejerman N. Atypical rolandic epilepsy. Epilepsia 2009; 50(suppl 7): 9–12.
10.1111/j.1528-1167.2009.02210.x
PubMed Web of Science® Google Scholar
4Clarke T, Strug LJ, Murphy PL, et al. High risk of reading disability and speech sound disorder in rolandic epilepsy families: case-control study. Epilepsia 2007; 48: 2258–2265.
10.1111/j.1528-1167.2007.01276.x
CAS PubMed Web of Science® Google Scholar
5Tovia E, Goldberg-Stern H, Ben Zeev B, et al. The prevalence of atypical presentations and comorbidities of benign childhood epilepsy with centrotemporal spikes. Epilepsia 2011; 52: 1483–1488.
10.1111/j.1528-1167.2011.03136.x
PubMed Web of Science® Google Scholar
6Kavros PM, Clarke T, Strug LJ, et al. Attention impairment in rolandic epilepsy: systematic review. Epilepsia 2008; 49: 1570–1580.
10.1111/j.1528-1167.2008.01610.x
CAS PubMed Web of Science® Google Scholar
7Vears DF, Tsai MH, Sadleir LG, et al. Clinical genetic studies in benign childhood epilepsy with centrotemporal spikes. Epilepsia 2012; 53: 319–324.
10.1111/j.1528-1167.2011.03368.x
PubMed Web of Science® Google Scholar
8Lemke JR, Lal D, Reinthaler EM, et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet 2013; 45: 1067–1072.
10.1038/ng.2728
CAS PubMed Web of Science® Google Scholar
9Lesca G, Rudolf G, Bruneau N, et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet 2013; 45: 1061–1066.
10.1038/ng.2726
CAS PubMed Web of Science® Google Scholar
10Carvill GL, Regan BM, Yendle SC, et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet 2013; 45: 1073–1076.
10.1038/ng.2727
CAS PubMed Web of Science® Google Scholar
11Lal D, Reinthaler EM, Schubert J, et al. DEPDC5 mutations in genetic focal epilepsies of childhood. Ann Neurol 2014; 75: 788–792.
10.1002/ana.24127
CAS PubMed Web of Science® Google Scholar
12Lal D, Reinthaler EM, Altmuller J, et al. RBFOX1 and RBFOX3 mutations in rolandic epilepsy. PLoS One 2013; 8: e73323.
10.1371/journal.pone.0073323
CAS PubMed Web of Science® Google Scholar
13Reinthaler EM, Lal D, Lebon S, et al. 16p11.2 600 kb duplications confer risk for typical and atypical rolandic epilepsy. Hum Mol Genet 2014; 23: 6069–6080.
10.1093/hmg/ddu306
CAS PubMed Web of Science® Google Scholar
14Winkelmann A, Maggio N, Eller J, et al. Changes in neural network homeostasis trigger neuropsychiatric symptoms. J Clin Invest 2014; 124: 696–711.
10.1172/JCI71472
CAS PubMed Web of Science® Google Scholar
15Meier JC, Semtner M, Winkelmann A, Wolfart J. Presynaptic mechanisms of neuronal plasticity and their role in epilepsy. Front Cell Neurosci 2014; 8: 164.
10.3389/fncel.2014.00164
CAS PubMed Web of Science® Google Scholar
16Luscher B, Fuchs T, Kilpatrick CL. GABAA receptor trafficking-mediated plasticity of inhibitory synapses. Neuron 2011; 70: 385–409.
10.1016/j.neuron.2011.03.024
CAS PubMed Web of Science® Google Scholar
17Galanopoulou AS. GABA(A) receptors in normal development and seizures: friends or foes? Curr Neuropharmacol 2008; 6: 1–20.
10.2174/157015908783769653
CAS PubMed Web of Science® Google Scholar
18Olsen RW, DeLorey TM, Gordey M, Kang MH. GABA receptor function and epilepsy. Adv Neurol 1999; 79: 499–510.
CAS PubMed Google Scholar
19De Deyn PP, Marescau B, MacDonald RL. Epilepsy and the GABA-hypothesis: a brief review and some examples. Acta Neurol Belg 1990; 90: 65–81.
PubMed Web of Science® Google Scholar
20Macdonald RL, Kang JQ, Gallagher MJ. GABAA receptor subunit mutations and genetic epilepsies. In: JL Noebels, M Avoli, MA Rogawski, et al, eds. Jasper's basic mechanisms of the epilepsies. 4th ed. Bethesda, MD: National Center for Biotechnology Information, 2012.
10.1093/med/9780199746545.003.0057
Google Scholar
21Allen AS, Berkovic SF, Cossette P, et al. De novo mutations in epileptic encephalopathies. Nature 2013; 501: 217–221.
10.1038/nature12439
CAS PubMed Web of Science® Google Scholar
22Schweizer C, Balsiger S, Bluethmann H, et al. The gamma 2 subunit of GABA(A) receptors is required for maintenance of receptors at mature synapses. Mol Cell Neurosci 2003; 24: 442–450.
10.1016/S1044-7431(03)00202-1
CAS PubMed Web of Science® Google Scholar
23Dejanovic B, Schwarz G. Neuronal nitric oxide synthase-dependent S-nitrosylation of gephyrin regulates gephyrin clustering at GABAergic synapses. J Neurosci 2014; 34: 7763–7768.
10.1523/JNEUROSCI.0531-14.2014
CAS PubMed Web of Science® Google Scholar
24Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010; 51: 676–685.
10.1111/j.1528-1167.2010.02522.x
PubMed Web of Science® Google Scholar
25Aicardi J, Chevrie JJ. Atypical benign partial epilepsy of childhood. Dev Med Child Neurol 1982; 24: 281–292.
10.1111/j.1469-8749.1982.tb13620.x
CAS PubMed Web of Science® Google Scholar
26Doose H, Hahn A, Neubauer BA, et al. Atypical "benign" partial epilepsy of childhood or pseudo-Lennox syndrome. Part II: family study. Neuropediatrics 2001; 32: 9–13.
CAS PubMed Web of Science® Google Scholar
27Hahn A, Pistohl J, Neubauer BA, Stephani U. Atypical "benign" partial epilepsy or pseudo-Lennox syndrome. Part I: symptomatology and long-term prognosis. Neuropediatrics 2001; 32: 1–8.
10.1055/s-2001-12216
CAS PubMed Web of Science® Google Scholar
28Hofman A, van Duijn CM, Franco OH, et al. The Rotterdam Study: 2012 objectives and design update. Eur J Epidemiol 2011; 26: 657–686.
10.1007/s10654-011-9610-5
PubMed Web of Science® Google Scholar
29Purcell SM, Moran JL, Fromer M, et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 2014; 506: 185–190.
10.1038/nature12975
CAS PubMed Web of Science® Google Scholar
30Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 2004; 11: 377–394.
10.1089/1066527041410418
CAS PubMed Web of Science® Google Scholar
31Liu X, Jian X, Boerwinkle E. dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat 2013; 34: E2393–E2402.
10.1002/humu.22376
CAS PubMed Web of Science® Google Scholar
32Jacob TC, Bogdanov YD, Magnus C, et al. Gephyrin regulates the cell surface dynamics of synaptic GABAA receptors. J Neurosci 2005; 25: 10469–10478.
10.1523/JNEUROSCI.2267-05.2005
CAS PubMed Web of Science® Google Scholar
33Dejanovic B, Semtner M, Ebert S, et al. Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses. PLoS Biol 2014; 12: e1001908.
10.1371/journal.pbio.1001908
PubMed Web of Science® Google Scholar
34Fukata M, Fukata Y, Adesnik H, et al. Identification of PSD-95 palmitoylating enzymes. Neuron 2004; 44: 987–996.
10.1016/j.neuron.2004.12.005
CAS PubMed Web of Science® Google Scholar
35Dejanovic B, Lal D, Catarino CB, et al. Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy. Neurobiol Dis 2014; 67: 88–96.
10.1016/j.nbd.2014.02.001
CAS PubMed Web of Science® Google Scholar
36Tanaka M, Olsen RW, Medina MT, et al. Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. Am J Hum Genet 2008; 82: 1249–1261.
10.1016/j.ajhg.2008.04.020
CAS PubMed Web of Science® Google Scholar
37Dibbens LM, Feng HJ, Richards MC, et al. GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum Mol Genet 2004; 13: 1315–1319.
10.1093/hmg/ddh146
CAS PubMed Web of Science® Google Scholar
38Miller PS, Aricescu AR. Crystal structure of a human GABAA receptor. Nature 2014; 512: 270–275.
10.1038/nature13293
CAS PubMed Web of Science® Google Scholar
39Kang JQ, Macdonald RL. The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence epilepsy and febrile seizures causes retention of alpha1beta2gamma2S receptors in the endoplasmic reticulum. J Neurosci 2004; 24: 8672–8677.
10.1523/JNEUROSCI.2717-04.2004
CAS PubMed Web of Science® Google Scholar
40Keller CA, Yuan X, Panzanelli P, et al. The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ. J Neurosci 2004; 24: 5881–5891.
10.1523/JNEUROSCI.1037-04.2004
CAS PubMed Web of Science® Google Scholar
41Fang C, Deng L, Keller CA, et al. GODZ-mediated palmitoylation of GABA(A) receptors is required for normal assembly and function of GABAergic inhibitory synapses. J Neurosci 2006; 26: 12758–12768.
10.1523/JNEUROSCI.4214-06.2006
CAS PubMed Web of Science® Google Scholar
42De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 2014; 515: 209–215.
10.1038/nature13772
CAS PubMed Web of Science® Google Scholar
43Johnston AJ, Kang JQ, Shen W, et al. A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes. Neurobiol Dis 2014; 64: 131–141.
10.1016/j.nbd.2013.12.013
CAS PubMed Web of Science® Google Scholar
44de Kovel CG, Trucks H, Helbig I, et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 2010; 133(pt 1): 23–32.
10.1093/brain/awp262
PubMed Web of Science® Google Scholar
45Lal D, Trucks H, Moller RS, et al. Rare exonic deletions of the RBFOX1 gene increase risk of idiopathic generalized epilepsy. Epilepsia 2013; 54: 265–271.
10.1111/epi.12084
CAS PubMed Web of Science® Google Scholar
46Moller RS, Weber YG, Klitten LL, et al. Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy. Epilepsia 2013; 54: 256–264.
10.1111/epi.12078
CAS PubMed Web of Science® Google Scholar
47Ottman R. Analysis of genetically complex epilepsies. Epilepsia 2005; 46(suppl 10): 7–14.
10.1111/j.1528-1167.2005.00350.x
PubMed Web of Science® Google Scholar
48Audenaert D, Schwartz E, Claeys KG, et al. A novel GABRG2 mutation associated with febrile seizures. Neurology 2006; 67: 687–690.
10.1212/01.wnl.0000230145.73496.a2
CAS PubMed Web of Science® Google Scholar
49Huang X, Hernandez CC, Hu N, Macdonald RL. Three epilepsy-associated GABRG2 missense mutations at the gamma+/beta- interface disrupt GABAA receptor assembly and trafficking by similar mechanisms but to different extents. Neurobiol Dis 2014; 68: 167–179.
10.1016/j.nbd.2014.04.015
CAS PubMed Web of Science® Google Scholar
50Fisher JL, Macdonald RL. Single channel properties of recombinant GABAA receptors containing gamma 2 or delta subtypes expressed with alpha 1 and beta 3 subtypes in mouse L929 cells. J Physiol 1997; 505(pt 2): 283–297.
10.1111/j.1469-7793.1997.283bb.x
CAS PubMed Web of Science® Google Scholar
51Angelotti TP, Macdonald RL. Assembly of GABAA receptor subunits: alpha 1 beta 1 and alpha 1 beta 1 gamma 2S subunits produce unique ion channels with dissimilar single-channel properties. J Neurosci 1993; 13: 1429–1440.
10.1523/JNEUROSCI.13-04-01429.1993
CAS PubMed Web of Science® Google Scholar
52Essrich C, Lorez M, Benson JA, et al. Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci 1998; 1: 563–571.
10.1038/2798
CAS PubMed Web of Science® Google Scholar
53Li RW, Yu W, Christie S, et al. Disruption of postsynaptic GABA receptor clusters leads to decreased GABAergic innervation of pyramidal neurons. J Neurochem 2005; 95: 756–770.
10.1111/j.1471-4159.2005.03426.x
CAS PubMed Web of Science® Google Scholar
54Rathenberg J, Kittler JT, Moss SJ. Palmitoylation regulates the clustering and cell surface stability of GABAA receptors. Mol Cell Neurosci 2004; 26: 251–257.
10.1016/j.mcn.2004.01.012
CAS PubMed Web of Science® Google Scholar
55Todd E, Gurba KN, Botzolakis EJ, et al. GABAA receptor biogenesis is impaired by the gamma2 subunit febrile seizure-associated mutation, GABRG2(R177G). Neurobiol Dis 2014; 69: 215–224.
10.1016/j.nbd.2014.05.013
CAS PubMed Web of Science® Google Scholar
56Mody I, Pearce RA. Diversity of inhibitory neurotransmission through GABA(A) receptors. Trends Neurosci 2004; 27: 569–575.
10.1016/j.tins.2004.07.002
CAS PubMed Web of Science® Google Scholar
57Reid CA, Kim T, Phillips AM, et al. Multiple molecular mechanisms for a single GABAA mutation in epilepsy. Neurology 2013; 80: 1003–1008.
10.1212/WNL.0b013e3182872867
CAS PubMed Web of Science® Google Scholar
58Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 2011; 16: 383–406.
10.1038/mp.2010.120
CAS PubMed Web of Science® Google Scholar
59Shen Q, Fuchs T, Sahir N, Luscher B. GABAergic control of critical developmental periods for anxiety- and depression-related behavior in mice. PloS One 2012; 7: e47441.
10.1371/journal.pone.0047441
CAS PubMed Web of Science® Google Scholar
60Laurie DJ, Wisden W, Seeburg PH. The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J Neurosci 1992; 12: 4151–4172.
10.1523/JNEUROSCI.12-11-04151.1992
CAS PubMed Web of Science® Google Scholar
61Noebels JL. The biology of epilepsy genes. Annu Rev Neurosci 2003; 26: 599–625.
10.1146/annurev.neuro.26.010302.081210
CAS PubMed Web of Science® Google Scholar
62Goldberg EM, Coulter DA. Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. Nat Rev Neurosci 2013; 14: 337–349.
10.1038/nrn3482
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume77, Issue6

June 2015

Pages 972-986

Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes

Abstract

Objective

Methods

Results

Interpretation

Supporting Information

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes

Abstract

Objective

Methods

Results

Interpretation

Supporting Information

References

Citing Literature

References

Related

Information