Pathway-driven discovery of epilepsy genes

Nature Neuroscience

Volumn 18, Issue 3, 2015, Pages 344-350

  Noebels, Jeffrey ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; ION CHANNEL; NERVE PROTEIN;

ARTICLE; EPILEPSY; EPILEPSY ASSOCIATED GENE; EXOME; GENE; GENE EXPRESSION; GENE LOCUS; GENE MUTATION; HUMAN; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; SEIZURE; SOMATIC MUTATION; SUPPRESSOR GENE; ANIMAL; BRAIN; GENE THERAPY; GENETIC PREDISPOSITION; GENETICS; GENOME; METABOLISM; MUTATION; NERVE TRACT; PATHOLOGY; PHYSIOLOGY; PROCEDURES;

ANIMALS; BRAIN; EPILEPSY; GENETIC PREDISPOSITION TO DISEASE; GENETIC THERAPY; GENOME; HUMANS; ION CHANNELS; MUTATION; NERVE TISSUE PROTEINS; NEURAL PATHWAYS;

EID: 84923698562     PISSN: 10976256     EISSN: 15461726     Source Type: Journal    
DOI: 10.1038/nn.3933     Document Type: Article

References (96)

1. Shoffner, J.M. et al. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61, 931-937 (1990).
2. Berg, A.T. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51, 676-685 (2010).
3. MacArthur, D.G. et al. Guidelines for investigating causality of sequence variants in human disease. Nature 508, 469-476 (2014).
4. Petrovski, S. et al. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet. 9, e1003709 (2013).
5. Knecht, C. & Krawczak, M. Molecular genetic epidemiology of human diseases: from patterns to predictions. Hum. Genet. 133, 425-430 (2014).
6. Katsonis, P. et al. Single nucleotide variations: biological impact and theoretical interpretation. Protein Sci. 23, 1650-1666 (2014).
7. Veltman, J.A. & Brunner, H.G. De novo mutations in human genetic disease. Nat. Rev. Genet. 13, 565-575 (2012).
8. Hoischen, A., Krumm, N. & Eichler, E.E. Prioritization of neurodevelopmental disease genes by discovery of new mutations. Nat. Neurosci. 17, 764-772 (2014).
9. Epi4K Consortium. et al. De novo mutations in epileptic encephalopathies. Nature 501, 217-221 (2013).
10. Yang, H., Wang, H. & Jaenisch, R. Generating genetically modified mice using CRISPR/Cas-mediated genome engineering. Nat. Protoc. 9, 1956-1968 (2014).
11. Yin, H. et al. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat. Biotechnol. 32, 551-553 (2014).
12. Velasco, I. et al. Generation of neurons from somatic cells of healthy individuals and neurological patients through induced pluripotency or direct conversion. Stem Cells 32, 2811-2817 (2014).
13. Liu, Y. et al. Dravet syndrome patient-derived neurons suggest a novel epilepsy mechanism. Ann. Neurol. 74, 128-139 (2013).
14. Steinlein, O.K. et al. A missense mutation in the neuronal nicotinic acetylcholine receptor ±4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat. Genet. 11, 201-203 (1995).
15. Tempel, B.L. et al. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science 237, 770-775 (1987).
16. De Jonghe, P. Molecular genetics of Dravet syndrome. Dev. Med. Child Neurol. 53 (suppl. 2), 7-10 (2011).
17. Hildebrand, M.S. et al. Recent advances in the molecular genetics of epilepsy. J. Med. Genet. 50, 271-279 (2013).
18. Hirose, S. et al. SCN1A testing for epilepsy: application in clinical practice. Epilepsia 54, 946-952 (2013).
19. Maheshwari, A. & Noebels, J.L. Monogenic models of absence epilepsy: windows into the complex balance between inhibition and excitation in thalamocortical microcircuits. in Genetics of Epilepsy (ed. Steinlein, O.K.) Prog. Brain Res. 213, 223-252 (2014).
20. Jasper's Basic Mechanisms of the Epilepsies 4th edn. (eds. Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W. & Delgado-Escueta, A.V.) (Oxford Univ. Press, 2012).
21. French, J.A. ILAE classification redux: ready for prime time? Epilepsy Curr. 14, 84-85 (2014).
22. Singh, N.A. et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat. Genet. 18, 25-29 (1998).
23. Cooper, E.C. Potassium channels (including KCNQ) and epilepsy. in Jasper's Basic Mechanisms of the Epilepsies 4th edn. (eds. Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W. & Delgado-Escueta, A.V.) (National Center for Biotechnology Information, Bethesda, Maryland, USA, 2012).
24. Claes, L.R. et al. De novo KCNQ2 mutations in patients with benign neonatal seizures. Neurology 63, 2155-2158 (2004).
25. Orhan, G. et al. Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy. Ann. Neurol. 75, 382-394 (2014).
26. Wallace, R.H. et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel β1 subunit gene SCN1B. Nat. Genet. 19, 366-370 (1998).
27. Brunklaus, A. & Zuberi, S.M. Dravet syndrome-from epileptic encephalopathy to channelopathy. Epilepsia 55, 979-984 (2014).
28. Kim, G.E. & Kaczmarek, L.K. Emerging role of the KCNT1 Slack channel in intellectual disability. Front. Cell. Neurosci. 8, 209 (2014).
29. Barcia, G. et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat. Genet. 44, 1255-1259 (2012).
30. Heron, S.E. et al. Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy. Nat. Genet. 44, 1188-1190 (2012).
31. Pearson, T.S. et al. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr. Neurol. Neurosci. Rep. 13, 342 (2013).
32. Landrum, M.J. et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 42, D980-D985 (2014).
33. Peñagarikano, O. et al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147, 235-246 (2011).
34. Ozkan, E.D. et al. Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons. Neuron 82, 1317-1333 (2014).
35. Palop, J.J. et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55, 697-711 (2007).
36. Lopera, F. et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. J. Am. Med. Assoc. 277, 793-799 (1997).
37. Zhu, P.J. et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-γ-mediated disinhibition. Cell 147, 1384-1396 (2011).
38. Heron, S.E. et al. PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. Am. J. Hum. Genet. 90, 152-160 (2012).
39. Heinzen, E.L. et al. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol. 13, 503-514 (2014).
40. Ortolano, S. et al. Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease. Mol. Brain 7, 7 (2014).
41. Matsuura, T. et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat. Genet. 26, 191-194 (2000).
42. Betancur, C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 1380, 42-77 (2011).
43. Liu, M. et al. Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc. Natl. Acad. Sci. USA 97, 865-870 (2000).
44. Ross, M.E. & Walsh, C.A. Human brain malformations and their lessons for neuronal migration. Annu. Rev. Neurosci. 24, 1041-1070 (2001).
45. Hartmann, H.A. et al. Selective localization of cardiac SCN5A sodium channels in limbic regions of rat brain. Nat. Neurosci. 2, 593-595 (1999).
46. Goldman, A.M. et al. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci. Transl. Med. 1, 2ra6 (2009).
47. Glasscock, E. et al. Kv1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction as a candidate mechanism for sudden unexplained death in epilepsy. J. Neurosci. 30, 5167-5175 (2010).
48. Qi, Y. et al. Hyper-SUMOylation of the Kv7 potassium channel diminishes the M-current leading to seizures and sudden death. Neuron 83, 1159-1171 (2014).
49. Klassen, T.L. et al. High-resolution molecular genomic autopsy reveals complex sudden unexpected death in epilepsy risk profile. Epilepsia 55, e6-e12 (2014).
50. Heinzen, E.L. et al. Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy. Am. J. Hum. Genet. 91, 293-302 (2012).
51. Wheeler, D.A. & Wang, L. From human genome to cancer genome: the first decade. Genome Res. 23, 1054-1062 (2013).
52. Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546-1558 (2013).
53. Alexandrov, L.B. & Stratton, M.R. Mutational signatures: the patterns of somatic mutations hidden in cancer genomes. Curr. Opin. Genet. Dev. 24, 52-60 (2014).
54. Hu, W.F., Chahrour, M.H. & Walsh, C.A. The diverse genetic landscape of neurodevelopmental disorders. Annu. Rev. Genomics Hum. Genet. 15, 195-213 (2014).
55. Jamuar, S.S. et al. Somatic mutations in cerebral cortical malformations. N. Engl. J. Med. 371, 733-743 (2014).
56. Lee, J.H. et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44, 941-945 (2012).
57. Cai, X. et al. Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain. Cell Reports 8, 1280-1289 (2014).
58. Fishell, G. & Heintz, N. The neuron identity problem: form meets function. Neuron 80, 602-612 (2013).
59. Gerfen, C.R., Paletzki, R. & Heintz, N. GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits. Neuron 80, 1368-1383 (2013).
60. Eberwine, J. et al. The promise of single-cell sequencing. Nat. Methods 11, 25-27 (2014).
61. Stephens, P.J. et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 486, 400-404 (2012).
62. Maheshwari, A. & Noebels, J.L. Monogenic models of absence epilepsy: windows into the complex balance between inhibition and excitation in thalamocortical microcircuits. Prog. Brain Res. 213, 223-252 (2014).
63. Brooks-Kayal, A.R. & Russek, S.J. Regulation of GABAA receptor gene expression and epilepsy. in Jasper's Basic Mechanisms of the Epilepsies 4th edn. (eds. Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W. & Delgado-Escueta, A.V.) (National Center for Biotechnology Information, Bethesda, Maryland, USA, 2012).
64. Houser, C.R. Do structural changes in GABA neurons give rise to the epileptic state? Adv. Exp. Med. Biol. 813, 151-160 (2014).
65. Petilla Interneuron Nomenclature Group. et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 9, 557-568 (2008).
66. Kepecs, A. & Fishell, G. Interneuron cell types are fit to function. Nature 505, 318-326 (2014).
67. Okaty, B.W. et al. Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. J. Neurosci. 29, 7040-7052 (2009).
68. Lancaster, E. & Dalmau, J. Neuronal autoantigens-pathogenesis, associated disorders and antibody testing. Nat. Rev. Neurosci. 8, 380-390 (2012).
69. Rossignol, E. et al. CaV 2.1 ablation in cortical interneurons selectively impairs fast-spiking basket cells and causes generalized seizures. Ann. Neurol. 74, 209-222 (2013).
70. Mark, M.D. et al. Delayed postnatal loss of P/Q-type calcium channels recapitulates the absence epilepsy, dyskinesia, and ataxia phenotypes of genomic Cacna1a mutations. J. Neurosci. 31, 4311-4326 (2011).
71. Maejima, T. et al. Postnatal loss of P/Q-type channels confined to rhombic-lip-derived neurons alters synaptic transmission at the parallel fiber to purkinje cell synapse and replicates genomic Cacna1a mutation phenotype of ataxia and seizures in mice. J. Neurosci. 33, 5162-5174 (2013).
72. Ogiwara, I. et al. Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome. Hum. Mol. Genet. 22, 4784-4804 (2013).
73. Chao, H.T. et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468, 263-269 (2010).
74. Zhang, W. et al. Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J. Neurosci. 34, 2754-2763 (2014).
75. Burgess, D.L. et al. β subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. Mol. Cell. Neurosci. 13, 293-311 (1999).
76. Zucchini, S. et al. Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology. PLoS ONE 9, e105521 (2014).
77. Henshall, D.C. MicroRNA and epilepsy: profiling, functions and potential clinical applications. Curr. Opin. Neurol. 27, 199-205 (2014).
78. Ule, J. et al. Nova regulates brain-specific splicing to shape the synapse. Nat. Genet. 37, 844-852 (2005).
79. St Laurent, G. et al. Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila. Nat. Struct. Mol. Biol. 20, 1333-1339 (2013).
80. Eom, T. et al. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. Elife 2, e00178 (2013).
81. Klassen, T. et al. Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell 145, 1036-1048 (2011).
82. Toledo-Rodriguez, M. et al. Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex. Cereb. Cortex 14, 1310-1327 (2004).
83. Glasscock, E. et al. Masking epilepsy by combining two epilepsy genes. Nat. Neurosci. 10, 1554-1558 (2007).
84. Marder, E. Neuromodulation of neuronal circuits: back to the future. Neuron 76, 1-11 (2012).
85. Marder, E. & Goaillard, J.M. Variability, compensation and homeostasis in neuron and network function. Nat. Rev. Neurosci. 7, 563-574 (2006).
86. Ganetzky, B. & Wu, C.F. Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing. J. Neurophysiol. 47, 501-514 (1982).
87. Frankel, W.N. et al. Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy. PLoS Genet. 10, e1004454 (2014).
88. Meisler, M.H., O'Brien, J.E. & Sharkey, L.M. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J. Physiol. (Lond.) 588, 1841-1848 (2010).
89. Miller, A.R. et al. Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Genes Brain Behav. 13, 163-172 (2014).
90. Howlett, I.C. et al. Drosophila as a model for intractable epilepsy: gilgamesh suppresses seizures in para(bss1) heterozygote flies. G3 (Bethesda) 3, 1399-1407 (2013).
91. Holth, J.K. et al. Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy. J. Neurosci. 33, 1651-1659 (2013).
92. Gheyara, A.L. et al. Tau reduction prevents disease in a mouse model of Dravet syndrome. Ann. Neurol. 76, 443-456 (2014).
93. Tomaselli, G.F. Cardiac Ito, KCNE2, and Brugada syndrome: promiscuous subunit interactions, or what happens in HEK cells stays in HEK cells? Heart Rhythm 7, 206-207 (2010).
94. Yu, F.H. et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat. Neurosci. 9, 1142-1149 (2006).
95. Zhang, Y. et al. Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J. Neurosci. 22, 6362-6371 (2002).
96. Sutherland, M.L. et al. Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression. Proc. Natl. Acad. Sci. USA 96, 2451-2455 (1999).