Genetic neurological channelopathies: Molecular genetics and clinical phenotypes

Journal of Neurology, Neurosurgery and Psychiatry

Volumn 87, Issue 1, 2016, Pages 37-48

  Spillane, J ^a,b   Kullmann, D M ^b,c   Hanna, M G ^b,c  

^a ROYAL FREE HOSPITAL   (United Kingdom)

^b NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

SODIUM CHANNEL NAV1.1; SODIUM CHANNEL NAV1.2;

ABSENCE; ANDERSEN SYNDROME; ATAXIA; AUTOSOMAL DOMINANT NOCTURNAL FRONTAL LOBE EPILEPSY; BENIGN FAMILIAL NEONATAL INFANTILE SEIZURE; CENTRAL NERVOUS SYSTEM; CEREBELLAR ATAXIA; CLINICAL FEATURE; CONGENITAL ANALGESIA; CONGENITAL MYASTHENIC SYNDROME; DISEASE ASSOCIATION; ELECTROPHYSIOLOGY; EPILEPSY; EPISODIC ATAXIA; ERYTHROMELALGIA; FAMILIAL EPISODIC PAIN SYNDROME; FAMILIAL HYPEREKPLEXIA; FOCAL EPILEPSY; GENE MUTATION; GENERALIZED EPILEPSY; GENERALIZED EPILEPSY WITH FEBRILE SEIZURE PLUS; GENETIC ASSOCIATION; HUMAN; HYPEREKPLEXIA; HYPOKALEMIC PERIODIC PARALYSIS; INFANTILE SPASM; MIGRAINE; MIGRATING PARTIAL SEIZURE OF INFANCY; MOLECULAR PATHOLOGY; MOTOR NEUROPATHY; MUSCLE CHANNELOPATHY; NEURONAL CHANNELOPATHY; NONHUMAN; PAIN; PAROXSYMAL EXTREME PAIN DISORDER; PATIENT CARE; PERIODIC PARALYSIS; PERIPHERAL NERVE HYPEREXCITABILITY; PERIPHERAL NEUROPATHY; PHENOTYPE; PRIMARY ERYTHROMELALGIA; PRIORITY JOURNAL; REVIEW; SCN2A GENE; SCNA1 GENE; SENSORY NEUROPATHY; SEVERE MYOCLONIC EPILEPSY IN INFANCY; SMALL FIBER NEUROPATHY; SODIUM CHANNEL MYOTONIA; SPINOCEREBELLAR ATAXIA; THOMSEN DISEASE; THYROTOXIC PERIODIC PARALYSIS; CENTRAL NERVOUS SYSTEM DISEASE; CHANNELOPATHY; GENETICS; MOLECULAR BIOLOGY; PATHOLOGY;

CENTRAL NERVOUS SYSTEM DISEASES; CHANNELOPATHIES; HUMANS; MOLECULAR BIOLOGY; PHENOTYPE;

EID: 84956602078     PISSN: 00223050     EISSN: 1468330X     Source Type: Journal    
DOI: 10.1136/jnnp-2015-311233     Document Type: Review

References (196)

1. Felix R. Channelopathies: ion channel defects linked to heritable clinical disorders. J Med Genet 2000;37:729-40.
2. Graves TD, Hanna MG. Neurological channelopathies. Postgrad Med J 2005;81:20-32.
3. Hübner CA, Jentsch TJ. Ion channel diseases. Hum Mol Genet 2002;11:2435-45.
4. Ryan DP, Ptácek LJ. Episodic neurological channelopathies. Neuron 2010;68:282-92.
5. Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001;68:1327-32.
6. Escayg A, Goldin AL. Sodium channel SCN1A and epilepsy: mutations and mechanisms. Epilepsia 2010;51:1650-8.
7. Ogiwara I, Miyamoto H, Morita N, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: A circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 2007;27:5903-14.
8. Stenhouse SA, Ellis R, Zuberi S. SCN1A genetic test for Dravet syndrome (severe myoclonic epilepsy of infancy and its clinical subtypes) for use in the diagnosis, prognosis, treatment and management of Dravet syndrome. PLoS Curr 2013;5. pii: ecurrents.eogt.c553b83d745dd79bfb61eaf35e522b0b.
9. Patino GA, Claes LR, Lopez-Santiago LF, et al. A functional null mutation of SCN1B in a patient with Dravet syndrome. J Neurosci 2009;29:10764-78.
10. Shi X, Yasumoto S, Kurahashi H, et al. Clinical spectrum of SCN2A mutations. Brain Dev 2012;34:541-5.
11. Ishii A, Kanaumi T, Sohda M, et al. Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy. Epilepsy Res 2014;108:420-32.
12. Yu FH, Mantegazza M, Westenbroek RE, et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 2006;9:1142-9.
13. Nakamura K, Kato M, Osaka H, et al. Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome. Neurology 2013;81:992-8.
14. Fukasawa T, Kubota T, Negoro T, et al. A case of recurrent encephalopathy with SCN2A missense mutation. Brain Dev 2015;37:631-4.
15. Fujiwara T, Sugawara T, Mazaki-Miyazaki E, et al. Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain 2003;126(Pt3):531-46.
16. Hirose S. Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy. Prog Brain Res 2014;213:55-85.
17. Allen AS, Berkovic SF, Cossette P, et al., EPI4K Consortium; Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 2013;501:217-21.
18. McTague A, Appleton R, Avula S, et al. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain 2013;136:1578-91.
19. Barcia G, Fleming MR, Deligniere A, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012;44:1255-9.
20. Veeramah KR, O'Brien JE, Meisler MH, et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet 2012;90:502-10.
21. Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012;71:15-25.
22. Milh M, Boutry-Kryza N, Sutera-Sardo J, et al. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2. Orphanet J Rare Dis 2013;8:80.
23. Slingerland AS, Hattersley AT. Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment. Ann Med 2005;37:186-95.
24. Gloyn AL, Pearson ER, Antcliff JF, et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 2004;350:1838-49.
25. Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain 1997;120(Pt3):479-90.
26. Sugawara T, Tsurubuchi Y, Agarwala KL, et al. A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci USA 2001;98:6384-9.
27. Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel β1 subunit gene SCN1B. Nat Genet 1998;19:366-70.
28. Escayg A, Heils A, MacDonald BT, et al. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus-and prevalence of variants in patients with epilepsy. Am J Hum Genet 2001;68:866-73.
29. Baulac S, Huberfeld G, Gourfinkel-An I, et al. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: A mutation in the gamma2-subunit gene. Nat Genet 2001;28:46-8.
30. Dibbens 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;13:1315-19.
31. Herlenius E, Heron SE, Grinton BE, et al. SCN2A mutations and benign familial neonatal-infantile seizures: The phenotypic spectrum. Epilepsia 2007;48:1138-42.
32. Heron SE, Crossland KM, Andermann E, et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 2002;360:851-2.
33. Gourfinkel-An I, Baulac S, Nabbout R, et al. Monogenic idiopathic epilepsies. Lancet Neurol 2004;3:209-18.
34. Ronen GM, Rosales TO, Connolly M, et al. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology 1993;43:1355-60.
35. Singh NA, Charlier C, Stauffer D, et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet 1998;18:25-9.
36. Charlier C, Singh NA, Ryan SG, et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 1998;18:53-5.
37. Biervert C, Schroeder BC, Kubisch C, et al. A potassium channel mutation in neonatal human epilepsy. Science 1998;279:403-6.
38. Hirose S, Zenri F, Akiyoshi H, et al. A novel mutation of KCNQ3 (c.925T->C) in a Japanese family with benign familial neonatal convulsions. Ann Neurol 2000;47:822-6.
39. Wang HS, Pan Z, Shi W, et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 1998;282:1890-3.
40. Du W, Bautista JF, Yang H, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 2005;37:733-8.
41. Chen Y, Lu J, Pan H, et al. Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol 2003;54:239-43.
42. Heron SE, Phillips HA, Mulley JC, et al. Genetic variation of CACNA1H in idiopathic generalized epilepsy. Ann Neurol 2004;55:595-6.
43. Maljevic S, Krampfl K, Cobilanschi J, et al. A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann Neurol 2006;59:983-7.
44. Tanaka 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;82:1249-61.
45. Gurba KN, Hernandez CC, Hu N, et al. GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating. J Biol Chem 2012;287:12083-97.
46. Cossette P, Liu L, Brisebois K, et al. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet 2002;31:184-9.
47. Lachance-Touchette P, Brown P, Meloche C, et al. Novel α1 and γ2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur J Neurosci 2011;34:237-49.
48. Pena SD, Coimbra RL. Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy. Clin Genet 2015;87:1-3.
49. Oldani A, Zucconi M, Asselta R, et al. Autosomal dominant nocturnal frontal lobe epilepsy. A video-polysomnographic and genetic appraisal of 40 patients and delineation of the epileptic syndrome. Brain 1998;121(Pt2):205-23.
50. Lemoine D, Jiang R, Taly A, et al. Ligand-gated ion channels: new insights into neurological disorders and ligand recognition. Chem Rev 2012;112:6285-318.
51. Steinlein OK, Mulley JC, Propping P, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 1995;11:201-3.
52. Leniger T, Kananura C, Hufnagel A, et al. A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy. Epilepsia 2003;44:981-5.
53. De Fusco M, Becchetti A, Patrignani A, et al. The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet 2000;26:275-6.
54. Kuryatov A, Gerzanich V, Nelson M, et al. Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca2+ permeability, conductance, and gating of human alpha4beta2 nicotinic acetylcholine receptors. J Neurosci 1997;17:9035-47.
55. Sáenz A, Galán J, Caloustian C, et al. Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene. Arch Neurol 1999;56:1004-9.
56. Rózycka A, Trzeciak WH. Genetic basis of autosomal dominant nocturnal frontal lobe epilepsy. J Appl Genet 2003;44:197-207.
57. Hoda JC, Gu W, Friedli M, et al. Human nocturnal frontal lobe epilepsy: pharmocogenomic profiles of pathogenic nicotinic acetylcholine receptor beta-subunit mutations outside the ion channel pore. Mol Pharmacol 2008;74:379-91.
58. Rodrigues-Pinguet NO, Pinguet TJ, Figl A, et al. Mutations linked to autosomal dominant nocturnal frontal lobe epilepsy affect allosteric Ca2+ activation of the alpha 4 beta 2 nicotinic acetylcholine receptor. Mol Pharmacol 2005;68:487-501.
59. Holland KD, Kearney JA, Glauser TA, et al. Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy. Neurosci Lett 2008;433:65-70.
60. Kullmann DM, Waxman SG. Neurological channelopathies: new insights into disease mechanisms and ion channel function. J Physiol 2010;588(Pt11):1823-7.
61. Chen TT, Klassen TL, Goldman AM, et al. Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy. Neurology 2013;80:1078-85.
62. Heinzen EL, Depondt C, Cavalleri GL, 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 2012;91:293-302.
63. Miceli F, Soldovieri MV, Ambrosino P, et al. Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits. Proc Natl Acad Sci 2013;110:4386-91.
64. Tomlinson SE, Rajakulendran S, Tan SV, et al. Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. J Neurol Neurosurg Psychiatry 2013;84:1107-12.
65. Graves TD, Cha YH, Hahn AF, et al., CINCH Investigators. Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation. Brain 2014;137(Pt4):1009-18.
66. Tomlinson SE, Hanna MG, Kullmann DM, et al. Clinical neurophysiology of the episodic ataxias: insights into ion channel dysfunction in vivo. Clin Neurophysiol 2009;120:1768-76.
67. Zuberi SM, Eunson LH, Spauschus A, et al. A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy. Brain 1999;122(Pt5):817-25.
68. Eunson LH, Rea R, Zuberi SM, et al. Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol 2000;48:647-56.
69. Browne DL, Gancher ST, Nutt JG, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet 1994;8:136-40.
70. Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol 2001;112:1575-85.
71. Adelman JP, Bond CT, Pessia M, et al. Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron 1995;15:1449-54.
72. Tomlinson SE, Tan SV, Kullmann DM, et al. Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1. Brain 2010;133(Pt12):3530-40.
73. D'Adamo MC, Gallenmüller C, Servettini I, et al. Novel phenotype associated with a mutation in the KCNA1(Kv1.1) gene. Front Physiol 2014;5:525.
74. Jen JC, Graves TD, Hess EJ, et al. Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 2007;130:2484-93.
75. Spacey SD, Materek LA, Szczygielski BI, et al. Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia. Arch Neurol 2005;62:314-16.
76. Imbrici P, Jaffe SL, Eunson LH, et al. Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain 2004;127(Pt12):2682-92.
77. Kinder S, Ossig C, Wienecke M, et al. Novel frameshift mutation in the CACNA1A gene causing a mixed phenotype of episodic ataxia and familiar hemiplegic migraine. Eur J Paediatr Neurol 2015;19:72-4.
78. Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology 2004;62:17-22.
79. Pietrobon D. Calcium channels and channelopathies of the central nervous system. Mol Neurobiol 2002;25:31-50.
80. Guida S, Trettel F, Pagnutti S, et al. Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2. Am J Hum Genet 2001;68:759-64.
81. Spacey SD, Hildebrand ME, Materek LA, et al. Functional implications of a novel EA2 mutation in the P/Q-type calcium channel. Ann Neurol 2004;56:213-20.
82. Wan J, Khanna R, Sandusky M, et al. CACNA1A mutations causing episodic and progressive ataxia alter channel trafficking and kinetics. Neurology 2005;64:2090-7.
83. Baloh RW. Episodic ataxias 1 and 2. Handb Clin 2012;103:595-602.
84. Strupp M, Kalla R, Claassen J, et al. A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology 2011;77:269-75.
85. Alviña K, Khodakhah K. The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia. J Neurosci 2010;30:7258-68.
86. Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 1997;15:62-9.
87. Schöls L, Krüger R, Amoiridis G, et al. Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds. J Neurol Neurosurg Psychiatry 1998;64:67-73.
88. Watase K, Barrett CF, Miyazaki T, et al. Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels. Proc Natl Acad Sci USA 2008;105:11987-92.
89. Jodice C, Mantuano E, Veneziano L, et al. Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. Hum Mol Genet 1997;6:1973-8.
90. Blumkin L, Leshinsky-Silver E, Michelson M, et al. Paroxysmal tonic upward gaze as a presentation of de-novo mutations in CACNA1A. Eur J Paediatr Neurol 2015;19:292-7.
91. Waters MF, Minassian NA, Stevanin G, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 2006;38:447-51.
92. Minassian NA, Lin MC, Papazian DM. Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13. J Physiol 2012;590(Pt7):1599-614.
93. Rudy B, McBain CJ. Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci 2001;24:517-26.
94. Lee YC, Durr A, Majczenko K, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol 2012;72:859-69.
95. Duarri A, Jezierska J, Fokkens M, et al. Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Ann Neurol 2012;72:870-80.
96. Ducros A, Tournier-Lasserve E, Bousser MG. The genetics of migraine. Lancet Neurol 2002;1:285-93.
97. Terwindt GM, Ophoff RA, Haan J, et al. Familial hemiplegic migraine: A clinical comparison of families linked and unlinked to chromosome 19.DMG RG. Cephalalgia 1996;16:153-5.
98. Pelzer N, Stam AH, Haan J, et al. Familial and sporadic hemiplegic migraine: diagnosis and treatment. Curr Treat Options Neurol 2013;15:13-27.
99. Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996;87:543-52.
100. De Fusco M, Marconi R, Silvestri L, et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 2003;33:192-6.
101. Dichgans M, Freilinger T, Eckstein G, et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 2005;366:371-7.
102. Athwal BS, Lennox GG, Elliott MA, et al. Acetazolamide responsiveness in familial hemiplegic migraine. Ann Neurol 1996;40:820-1.
103. Jen JC. Familial Hemiplegic Migraine. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. Gene Reviews®. Seattle, WA: University of Washington, Seattle, 1993-2015. http://www.ncbi.nlm.nih.gov/books/NBK1388.
104. Zhou L, Chillag KL, Nigro MA. Hyperekplexia: A treatable neurogenetic disease. Brain Dev 2002;24:669-74.
105. Shiang R, Ryan SG, Zhu YZ, et al. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet 1993;5:351-8.
106. Langosch D, Laube B, Rundström N, et al. Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J 1994;13:4223-8.
107. Chung SK, Bode A, Cushion TD, et al. GLRB is the third major gene of effect in hyperekplexia. Hum Mol Genet 2013;22:927-40.
108. Carta E, Chung SK, James VM, et al. Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease. J Biol Chem 2012;287:28975-85.
109. Eulenburg V, Becker K, Gomeza J, et al. Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem Biophys Res Commun 2006;348:400-5.
110. Rees MI, Harvey K, Pearce BR, et al. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet 2006;38:801-6.
111. Tijssen MA, Schoemaker HC, Edelbroek PJ, et al. The effects of clonazepam and vigabatrin in hyperekplexia. J Neurol Sci 1997;149:63-7.
112. Fischer TZ, Waxman SG. Familial pain syndromes from mutations of the NaV1.7 sodium channel. Ann N Y Acad Sci 2010;1184:196-207.
113. Yuan J, Matsuura E, Higuchi Y, et al. Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation. Neurology 2013;80:1641-9.
114. Van Genderen PJ, Michiels JJ, Drenth JP. Hereditary erythromelalgia and acquired erythromelalgia. Am J Med Genet 1993;45:530-1.
115. Bennett DL, Woods CG. Painful and painless channelopathies. Lancet Neurol 2014;13:587-99.
116. Yang Y, Wang Y, Li S, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythromelalgia. J Med Genet 2004;41:171-4.
117. Dib-Hajj SD, Rush AM, Cummins TR, et al. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 2005;128(Pt8):1847-54.
118. Cummins TR, Dib-Hajj SD, Waxman SG. Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci 2004;24:8232-6.
119. Waxman SG, Merkies IS, Gerrits MM, et al. Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use. Lancet Neurol 2014;13:1152-60.
120. Fertleman CR, Ferrie CD. What's in a name-familial rectal pain syndrome becomes paroxysmal extreme pain disorder. J Neurol Neurosurg Psychiatry 2006;77:1294-5.
121. Fertleman CR, Baker MD, Parker KA, et al. SCN9A mutations in paroxysmal extreme pain disorder: Allelic variants underlie distinct channel defects and phenotypes. Neuron 2006;52:767-74.
122. Fertleman CR, Ferrie CD, Aicardi J, et al. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology 2007;69:586-95.
123. Choi JS, Boralevi F, Brissaud O, et al. Paroxysmal extreme pain disorder: A molecular lesion of peripheral neurons. Nat Rev Neurol 2011;7:51-5.
124. Nathan A, Rose JB, Guite JW, et al. Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment. Pediatrics 2005;115:e504-7.
125. Cregg R, Cox JJ, Bennett DL, et al. Mexiletine as a treatment for primary erythromelalgia: normalization of biophysical properties of mutant L858F NaV 1.7 sodium channels. Br J Pharmacol 2014;171:4455-63.
126. Cox JJ, Reimann F, Nicholas AK, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006;444:894-8.
127. Goldberg YP, MacFarlane J, MacDonald ML, et al. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 2007;71:311-19.
128. Leipold E, Liebmann L, Korenke GC, et al. A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat Genet 2013;45:1399-404.
129. Faber CG, Hoeijmakers JG, Ahn HS, et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol 2012;71:26-39.
130. Faber CG, Lauria G, Merkies IS, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci USA 2012;109:19444-9.
131. Huang J, Han C, Estacion M, et al., PROPANE Study Group. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy. Brain 2014;137(Pt6):1627-42.
132. Kremeyer B, Lopera F, Cox JJ, et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 2010;66:671-80.
133. Bautista DM, Jordt SE, Nikai T, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 2006;124:1269-82.
134. Zhang XY, Wen J, Yang W, et al. Gain-of-function mutations in SCN11A cause familial episodic pain. Am J Hum Genet 2013;93:957-66.
135. Zimon M, Baets J, Auer-Grumbach M, et al. Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies. Brain 2010;133(Pt6):1798-809.
136. Nilius B, Owsianik G. Channelopathies converge on TRPV4. Nat Genet 2010;42:98-100.
137. Landouré G, Zdebik AA, Martinez TL, et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat Genet 2010;42:170-4.
138. DeLong R, Siddique T. A large New England kindred with autosomal dominant neurogenic scapuloperoneal amyotrophy with unique features. Arch Neurol 1992;49:905-8.
139. Deng HX, Klein CJ, Yan J, et al. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nat Genet 2010;42:165-9.
140. Auer-Grumbach M, Olschewski A, Papić L, et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nat Genet 2010;42:160-4.
141. Wuttke TV, Jurkat-Rott K, Paulus W, et al. Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations. Neurology 2007;69:2045-53.
142. Gancher ST, Nutt JG. Autosomal dominant episodic ataxia: A heterogeneous syndrome. Mov Disord 1986;1:239-53.
143. Dedek K, Kunath B, Kananura C, et al. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci USA 2001;98:12272-7.
144. Finlayson S, Beeson D, Palace J. Congenital myasthenic syndromes: An update. Pract Neurol 2013;13:80-91.
145. Burke G, Cossins J, Maxwell S, et al. Distinct phenotypes of congenital acetylcholine receptor deficiency. Neuromuscul Disord 2004;14:356-64.
146. Barišić N, Chaouch A, Müller JS, et al. Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes. Eur J Paediatr Neurol 2011;15:189-96.
147. Chaouch A, Müller JS, Guergueltcheva V, et al. A retrospective clinical study of the treatment of slow-channel congenital myasthenic syndrome. J Neurol 2012;259:474-81.
148. Horga A, Raja Rayan DL, Matthews E, et al. Prevalence study of genetically defined skeletal muscle channelopathies in England. Neurology 2013;80:1472-5.
149. Koch MC, Steinmeyer K, Lorenz C, et al. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 1992;257:797-800.
150. Cannon SC. Voltage-sensor mutations in channelopathies of skeletal muscle. J Physiol 2010;588:1887-95.
151. George AL Jr, Sloan-Brown K, Fenichel GM, et al. Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita. Hum Mol Genet 1994;3:2071-2.
152. Heine R, George AL Jr, Pika U, et al. Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. Hum Mol Genet 1994;3:1123-8.
153. Fialho D, Schorge S, Pucovska U, et al. Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions. Brain 2007;130(Pt12):3265-74.
154. George AL Jr, Crackower MA, Abdalla JA, et al. Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). Nat Genet 1993;3:305-10.
155. Raja Rayan DL, Haworth A, Sud R, et al. A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1. Neurology 2012;78:1953-8.
156. Raja Rayan DL, Hanna MG. Skeletal muscle channelopathies: nondystrophic myotonias and periodic paralysis. Curr Opin Neurol 2010;23:466-76.
157. Matthews E, Manzur AY, Sud R, et al. Stridor as a neonatal presentation of skeletal muscle sodium channelopathy. Arch Neurol 2011;68:127-9.
158. Trivedi JR, Bundy B, Statland J, et al., CINCH Consortium. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain 2013;136(Pt7):2189-200.
159. Matthews E, Tan SV, Fialho D, et al. What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed. Neurology 2008;70:50-3.
160. Furby A, Vicart S, Camdessanché JP, et al. Heterozygous CLCN1 mutations can modulate phenotype in sodium channel myotonia. Neuromuscul Disord 2014;24:953-9.
161. Desaphy JF, De Luca A, Tortorella P, et al. Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative. Neurology 2001;57:1849-57.
162. Wang GK, Russell C, Wang SY. Mexiletine block of wild-type and inactivation-deficient human skeletal muscle hNav1.4 Na+ channels. J Physiol 2004;554(Pt3):621-33.
163. Statland JM, Bundy BN, Wang Y, et al. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: A randomized controlled trial. JAMA 2012;308:1357-65.
164. Markhorst JM, Stunnenberg BC, Ginjaar IB, et al. Clinical experience with long-term acetazolamide treatment in children with nondystrophic myotonias: A three-case report. Pediatr Neurol 2014;51:537-41.
165. Eguchi H, Tsujino A, Kaibara M, et al. Acetazolamide acts directly on the human skeletal muscle chloride channel. Muscle Nerve 2006;34:292-7.
166. Novak KR, Norman J, Mitchell JR, et al. Sodium channel slow inactivation as a therapeutic target for myotonia congenita. Ann Neurol 2015;77:320-32.
167. Links TP, Zwarts MJ, Wilmink JT, et al. Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects. Brain 1990;113(Pt6):1873-89.
168. Jurkat-Rott K, Lehmann-Horn F, Elbaz A, et al. A calcium channel mutation causing hypokalemic periodic paralysis. Hum Mol Genet 1994;3:1415-19.
169. Ptácek LJ, Tawil R, Griggs RC, et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 1994;77:863-8.
170. Miller TM, Dias da Silva MR, Miller HA, et al. Correlating phenotype and genotype in the periodic paralyses. Neurology 2004;63:1647-55.
171. Matthews E, Labrum R, Sweeney MG, et al. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology 2009;72:1544-7.
172. Sokolov S, Scheuer T, Catterall WA. Gating pore current in an inherited ion channelopathy. Nature 2007;446:76-8.
173. Geukes Foppen RJ, van Mil HG, van Heukelom JS. Effects of chloride transport on bistable behaviour of the membrane potential in mouse skeletal muscle. J Physiol 2002;542(Pt1):181-91.
174. Struyk AF, Cannon SC. A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. J Gen Physiol 2007;130:11-20.
175. Jurkat-Rott K, Weber MA, Fauler M, et al. K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. Proc Natl Acad Sci USA 2009;106:4036-41.
176. Wu F, Mi W, Cannon SC. Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis. Neurology 2013;80:1110-16.
177. Suetterlin K, Männikkö R, Hanna MG. Muscle channelopathies: recent advances in genetics, pathophysiology and therapy. Curr Opin Neurol 2014;27: 583-90.
178. Cannon SC, Brown RH Jr, Corey DP. A sodium channel defect in hyperkalemic periodic paralysis: Potassium-induced failure of inactivation. Neuron 1991;6:619-26.
179. Lehmann-Horn F, Küther G, Ricker K, et al. Adynamia episodica hereditaria with myotonia: A non-inactivating sodium current and the effect of extracellular pH. Muscle Nerve 1987;10:363-74.
180. Cummins TR, Zhou J, Sigworth FJ, et al. Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis. Neuron 1993;10:667-78.
181. Cannon SC, Brown RH Jr, Corey DP. Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys J 1993;65:270-88.
182. Nguyen HL, Pieper GH, Wilders R. Andersen-Tawil syndrome: clinical and molecular aspects. Int J Cardiol 2013;170:1-16.
183. Zhang L, Benson DW, Tristani-Firouzi M, et al. Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation 2005;111:2720-6.
184. Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurother J Am Soc Exp Neurother 2007;4:233-7.
185. Tawil R, Ptacek LJ, Pavlakis SG, et al. Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol 1994;35:326-30.
186. Plaster NM, Tawil R, Tristani-Firouzi M, et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 2001;105:511-19.
187. Haruna Y, Kobori A, Makiyama T, et al. Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome. Hum Mutat 2007;28:208.
188. Kokunai Y, Nakata T, Furuta M, et al. A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir2.1. Neurology 2014;82:1058-64.
189. Hanna MG, Stewart J, Schapira AH, et al. Salbutamol treatment in a patient with hyperkalaemic periodic paralysis due to a mutation in the skeletal muscle sodium channel gene (SCN4A). J Neurol Neurosurg Psychiatry 1998;65:248-50.
190. Links TP, Zwarts MJ, Oosterhuis HJ. Improvement of muscle strength in familial hypokalaemic periodic paralysis with acetazolamide. J Neurol Neurosurg Psychiatry 1988;51:1142-5.
191. Tawil R, McDermott MP, Brown R Jr, et al. Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. Ann Neurol 2000;47:46-53.
192. Ligtenberg JJ, Van Haeften TW, Van Der Kolk LE, et al. Normal insulin release during sustained hyperglycaemia in hypokalaemic periodic paralysis: role of the potassium channel opener pinacidil in impaired muscle strength. Clin Sci (Lond) 1996;91:583-9.
193. Tan SV, Matthews E, Barber M, et al. Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies. Ann Neurol 2011;69:328-40.
194. Drost G, Stunnenberg BC, Trip J, et al. Myotonic discharges discriminate chloride from sodium muscle channelopathies. Neuromuscul Disord 2015;25:73-80.
195. Morrow JM, Matthews E, Raja Rayan DL, et al. Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias. Neuromuscul Disord 2013;23:637-46.
196. Ryan DP, da Silva MRD, Soong TW, et al. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell 2010;140:88-98.