As noted in the separate introduction to this special topic section, episodic and electrical disorders can appear quite different clinically and yet share many overlapping features, including attack precipitants, therapeutic responses, natural history, and the types of genes that cause many of the genetic forms (i.e., ion channel genes). Thus, as we mapped and attempted to clone genes causing other episodic disorders, ion channels were always outstanding candidates when they mapped to the critical region of linkage in such a family. However, some of these disorders do not result from mutations in channels. This realization has opened up large and exciting new areas for the pathogenesis of these disorders. In some cases, the mutations occur in genes of unknown function or without understanding of molecular pathogenesis. Recently, emerging insights into a fascinating group of episodic movement disorders, the paroxysmal dyskinesias, and study of the causative genes and proteins are leading to the emerging concept of episodic electric disorders resulting from synaptic dysfunction. Much work remains to be done, but the field is evolving rapidly. As it does, we have come to realize that the molecular pathogenesis of electrical and episodic disorders is more complex than a scenario in which such disorders are simply due to mutations in the primary determinants of membrane excitability (channels).


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Ptacek LJ, Fu YH. 1.  2002. Molecular biology of episodic movement disorders. Adv. Neurol. 89:453–58 [Google Scholar]
  2. Ryan DP, Ptáček LJ. 2.  2010. Episodic neurological channelopathies. Neuron 68:282–92 [Google Scholar]
  3. Kertesz A. 3.  1967. Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied. Neurology 17:680–90 [Google Scholar]
  4. Bruno MK, Hallett M, Gwinn-Hardy K, Sorensen B, Considine E. 4.  et al. 2004. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 63:2280–87 [Google Scholar]
  5. Lee HY, Huang Y, Bruneau N, Roll P, Roberson ED. 5.  et al. 2012. Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions. Cell Rep. 1:2–12 [Google Scholar]
  6. Swoboda KJ, Soong B, McKenna C, Brunt ER, Litt M. 6.  et al. 2000. Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies. Neurology 55:224–30 [Google Scholar]
  7. Mount LA, Reback S. 7.  1940. Familial paroxysmal choreoathetosis: preliminary report on a hitherto undescribed clinical syndrome. Arch. Neurol. Psychiat. 44:841–47 [Google Scholar]
  8. Bruno MK, Lee HY, Auburger GW, Friedman A, Nielsen JE. 8.  et al. 2007. Genotype-phenotype correlation of paroxysmal nonkinesigenic dyskinesia. Neurology 68:1782–89 [Google Scholar]
  9. Lance JW. 9.  1977. Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Ann. Neurol. 2:285–93 [Google Scholar]
  10. Bhatia KP. 10.  2011. Paroxysmal dyskinesias. Mov. Disord. 26:1157–65 [Google Scholar]
  11. Charlesworth G, Bhatia KP, Wood NW. 11.  2013. The genetics of dystonia: new twists in an old tale. Brain 136:2017–37 [Google Scholar]
  12. Weber YG, Lerche H. 12.  2009. Genetics of paroxysmal dyskinesias. Curr. Neurol. Neurosci. Rep. 9:206–11 [Google Scholar]
  13. Mehta SH, Morgan JC, Sethi KD. 13.  2009. Paroxysmal dyskinesias. Curr. Treat. Options Neurol. 11:170–78 [Google Scholar]
  14. Fuchs T, Ozelius LJ. 14.  2011. Genetics of dystonia. Semin. Neurol. 31:441–48 [Google Scholar]
  15. Skradski SL, White HS, Ptáček LJ. 15.  1998. Genetic mapping of a locus (mass1) causing audiogenic seizures in mice. Genomics 49:188–92 [Google Scholar]
  16. Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptáček LJ. 16.  2001. A novel gene causing a Mendelian audiogenic mouse epilepsy. Neuron 31:537–44 [Google Scholar]
  17. Klein BD, Fu YH, Ptacek LJ, White HS. 17.  2005. Auditory deficits associated with the Frings Mgr1 (Mass1) mutation in mice. Dev. Neurosci. 27:321–32 [Google Scholar]
  18. Deleted in proof
  19. Johnson KR, Zheng QY, Weston MD, Ptacek LJ, Noben-Trauth K. 19.  2005. The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics 85:582–90 [Google Scholar]
  20. Nakayama J, Hamano K, Iwasaki N, Nakahara S, Horigome Y. 20.  et al. 2000. Significant evidence for linkage of febrile seizures to chromosome 5q14–q15. Hum. Mol. Genet. 9:87–91 [Google Scholar]
  21. Deprez L, Claes LR, Claeys KG, Audenaert D, Van Dyck T. 21.  et al. 2006. Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3–q23.1 and no MASS1 mutation. Hum. Genet. 118:618–25 [Google Scholar]
  22. Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K. 22.  et al. 2002. A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann. Neurol. 52:654–57 [Google Scholar]
  23. Bonnet C, El-Amraoui A. 23.  2012. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches. Curr. Opin. Neurol. 25:42–49 [Google Scholar]
  24. Yan D, Liu XZ. 24.  2010. Genetics and pathological mechanisms of Usher syndrome. J. Hum. Genet. 55:327–35 [Google Scholar]
  25. Besnard T, Vache C, Baux D, Larrieu L, Abadie C. 25.  et al. 2012. Non-USH2A mutations in USH2 patients. Hum. Mutat. 33:504–10 [Google Scholar]
  26. Ebermann I, Wiesen MH, Zrenner E, Lopez I, Pigeon R. 26.  et al. 2009. GPR98 mutations cause Usher syndrome type 2 in males. J. Med. Genet. 46:277–80 [Google Scholar]
  27. Garcia-Garcia G, Besnard T, Baux D, Vache C, Aller E. 27.  et al. 2013. The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort. Mol. Vis. 19:367–73 [Google Scholar]
  28. Hilgert N, Kahrizi K, Dieltjens N, Bazazzadegan N, Najmabadi H. 28.  et al. 2009. A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. J. Med. Genet. 46:272–76 [Google Scholar]
  29. Hmani-Aifa M, Benzina Z, Zulfiqar F, Dhouib H, Shahzadi A. 29.  et al. 2009. Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family. Eur. J. Hum. Genet. 17:474–82 [Google Scholar]
  30. Le Quesne Stabej P, Saihan Z, Rangesh N, Steele-Stallard HB, Ambrose J. 30.  et al. 2012. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. J. Med. Genet. 49:27–36 [Google Scholar]
  31. Weston MD, Luijendijk MW, Humphrey KD, Moller C, Kimberling WJ. 31.  2004. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am. J. Hum. Genet. 74:357–66 [Google Scholar]
  32. Ebermann I, Phillips JB, Liebau MC, Koenekoop RK, Schermer B. 32.  et al. 2010. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome. J. Clin. Investig. 120:1812–23 [Google Scholar]
  33. McMillan DR, Kayes-Wandover KM, Richardson JA, White PC. 33.  2002. Very large G protein–coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J. Biol. Chem. 277:785–92 [Google Scholar]
  34. Scheel H, Tomiuk S, Hofmann K. 34.  2002. A common protein interaction domain links two recently identified epilepsy genes. Hum. Mol. Genet. 11:1757–62 [Google Scholar]
  35. Kalachikov S, Evgrafov O, Ross B, Winawer M, Barker-Cummings C. 35.  et al. 2002. Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat. Genet. 30:335–41 [Google Scholar]
  36. Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Saenz A, Poza JJ. 36.  et al. 2002. Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum. Mol. Genet. 11:1119–28 [Google Scholar]
  37. Yagi H, Takamura Y, Yoneda T, Konno D, Akagi Y. 37.  et al. 2005. Vlgr1 knockout mice show audiogenic seizure susceptibility. J. Neurochem. 92:191–202 [Google Scholar]
  38. McMillan DR, White PC. 38.  2004. Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol. Cell. Neurosci. 26:322–29 [Google Scholar]
  39. Grati M, Shin JB, Weston MD, Green J, Bhat MA. 39.  et al. 2012. Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the Usher syndrome protein network. J. Neurosci. 32:14288–93 [Google Scholar]
  40. McGee J, Goodyear RJ, McMillan DR, Stauffer EA, Holt JR. 40.  et al. 2006. The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles. J. Neurosci. 26:6543–53 [Google Scholar]
  41. Shin D, Lin S-T, Fu Y-H, Ptáček LJ. 41.  2013. MASS1 regulates MAG expression via Gαs/Gαq-mediated PKA/PKC pathways. PNAS 110:19101–6 [Google Scholar]
  42. Shibasaki H, Hallett M. 42.  2005. Electrophysiological studies of myoclonus. Muscle Nerve 31:157–74 [Google Scholar]
  43. Asmus F, Zimprich A, Tezenas Du Montcel S, Kabus C, Deuschl G. 43.  et al. 2002. Myoclonus-dystonia syndrome: ϵ-sarcoglycan mutations and phenotype. Ann. Neurol. 52:489–92 [Google Scholar]
  44. Zimprich A, Grabowski M, Asmus F, Naumann M, Berg D. 44.  et al. 2001. Mutations in the gene encoding ϵ-sarcoglycan cause myoclonus-dystonia syndrome. Nat. Genet. 29:66–69 [Google Scholar]
  45. Russell JF, Steckley JL, Coppola G, Hahn AF, Howard MA. 45.  et al. 2012. Familial cortical myoclonus with a mutation in NOL3. Ann. Neurol. 72:175–83 [Google Scholar]
  46. Gulesserian T, Engidawork E, Yoo BC, Cairns N, Lubec G. 46.  2001. Alteration of caspases and other apoptosis regulatory proteins in Down syndrome. J. Neural Transm. Suppl. 2001:163–79 [Google Scholar]
  47. Koseki T, Inohara N, Chen S, Nunez G. 47.  1998. ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. PNAS 95:5156–60 [Google Scholar]
  48. Shelke RR, Leeuwenburgh C. 48.  2003. Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain. FASEB J. 17:494–96 [Google Scholar]
  49. Chou JJ, Matsuo H, Duan H, Wagner G. 49.  1998. Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment. Cell 94:171–80 [Google Scholar]
  50. Zhou P, Chou J, Olea RS, Yuan J, Wagner G. 50.  1999. Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction. PNAS 96:11265–70 [Google Scholar]
  51. Donath S, Li P, Willenbockel C, Al-Saadi N, Gross V. 51.  et al. 2006. Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic stress. Circulation 113:1203–12 [Google Scholar]
  52. Engidawork E, Gulesserian T, Yoo BC, Cairns N, Lubec G. 52.  2001. Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease. Biochem. Biophys. Res. Commun. 281:84–93 [Google Scholar]
  53. Nam YJ, Mani K, Ashton AW, Peng CF, Krishnamurthy B. 53.  et al. 2004. Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions. Mol. Cell 15:901–12 [Google Scholar]
  54. Macerollo A, Mencacci NE, Erro R, Cordivari C, Edwards MJ. 54.  et al. 2014. Screening of mutations in NOL3 in a myoclonic syndromes series. J. Neurol. 261:1830–31 [Google Scholar]
  55. Eising E, de Vries B, Ferrari MD, Terwindt GM, van den Maagdenberg AM. 55.  2013. Pearls and pitfalls in genetic studies of migraine. Cephalalgia 33:614–25 [Google Scholar]
  56. Weir GA, Cader MZ. 56.  2011. New directions in migraine. BMC Med. 9:116 [Google Scholar]
  57. Zameel Cader M. 57.  2013. The molecular pathogenesis of migraine: new developments and opportunities. Hum. Mol. Genet. 22:R39–44 [Google Scholar]
  58. de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM. 58.  2009. Molecular genetics of migraine. Hum. Genet. 126:115–32 [Google Scholar]
  59. Di Lorenzo C, Grieco GS, Santorelli FM. 59.  2012. Migraine headache: a review of the molecular genetics of a common disorder. J. Headache Pain 13:571–80 [Google Scholar]
  60. Silberstein SD, Dodick DW. 60.  2013. Migraine genetics: part II. Headache 53:1218–29 [Google Scholar]
  61. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ. 61.  et al. 1996. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–52 [Google Scholar]
  62. Terwindt G, Kors E, Haan J, Vermeulen F, van den Maagdenberg A. 62.  et al. 2002. Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine. Arch. Neurol. 59:1016–18 [Google Scholar]
  63. De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L. 63.  et al. 2003. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat. Genet. 33:192–96 [Google Scholar]
  64. Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J. 64.  et al. 2003. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann. Neurol. 54:360–66 [Google Scholar]
  65. Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B. 65.  et al. 2005. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 366:371–77 [Google Scholar]
  66. Vahedi K, Depienne C, Le Fort D, Riant F, Chaine P. 66.  et al. 2009. Elicited repetitive daily blindness: a new phenotype associated with hemiplegic migraine and SCN1A mutations. Neurology 72:1178–83 [Google Scholar]
  67. Brennan KC, Bates EA, Shapiro RE, Zyuzin J, Hallows WC. 67.  et al. 2013. Casein kinase Iδ mutations in familial migraine and advanced sleep phase. Sci. Transl. Med. 5:183ra156 [Google Scholar]
  68. Xu Y, Padiath QS, Shapiro RE, Jones CR, Wu SC. 68.  et al. 2005. Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature 434:640–44 [Google Scholar]
  69. Knippschild U, Gocht A, Wolff S, Huber N, Lohler J, Stoter M. 69.  2005. The casein kinase 1 family: participation in multiple cellular processes in eukaryotes. Cell. Signal. 17:675–89 [Google Scholar]
  70. Knippschild U, Kruger M, Richter J, Xu P, Garcia-Reyes B. 70.  et al. 2014. The CK1 family: contribution to cellular stress response and its role in carcinogenesis. Front. Oncol. 4:96 [Google Scholar]
  71. Charles AC, Baca SM. 71.  2013. Cortical spreading depression and migraine. Nat. Rev. Neurol. 9:637–44 [Google Scholar]
  72. Contreras JE, Sanchez HA, Eugenin EA, Speidel D, Theis M. 72.  et al. 2002. Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. PNAS 99:495–500 [Google Scholar]
  73. Stout CE, Costantin JL, Naus CC, Charles AC. 73.  2002. Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J. Biol. Chem. 277:10482–88 [Google Scholar]
  74. Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR. 74.  2003. Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J. Neurosci. 23:3588–96 [Google Scholar]
  75. Cooper CD, Lampe PD. 75.  2002. Casein kinase 1 regulates connexin-43 gap junction assembly. J. Biol. Chem. 277:44962–68 [Google Scholar]
  76. Marquez-Rosado L, Solan JL, Dunn CA, Norris RP, Lampe PD. 76.  2012. Connexin43 phosphorylation in brain, cardiac, endothelial and epithelial tissues. Biochim. Biophys. Acta 1818:1985–992 [Google Scholar]
  77. Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC. 77.  2003. Plasma membrane channels formed by connexins: their regulation and functions. Physiol. Rev. 83:1359–400 [Google Scholar]
  78. Sarrouilhe D, Dejean C, Mesnil M. 78.  2014. Involvement of gap junction channels in the pathophysiology of migraine with aura. Front. Physiol. 5:78 [Google Scholar]
  79. Solan JL, Lampe PD. 79.  2009. Connexin43 phosphorylation: structural changes and biological effects. Biochem. J. 419:261–72 [Google Scholar]
  80. Lampe PD, Lau AF. 80.  2004. The effects of connexin phosphorylation on gap junctional communication. Int. J. Biochem. Cell Biol. 36:1171–86 [Google Scholar]
  81. Solan JL, Lampe PD. 81.  2005. Connexin phosphorylation as a regulatory event linked to gap junction channel assembly. Biochim. Biophys. Acta 1711:154–63 [Google Scholar]
  82. Lampe PD, Cooper CD, King TJ, Burt JM. 82.  2006. Analysis of Connexin43 phosphorylated at S325, S328 and S330 in normoxic and ischemic heart. J. Cell Sci. 119:3435–42 [Google Scholar]
  83. Theis M, Jauch R, Zhuo L, Speidel D, Wallraff A. 83.  et al. 2003. Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin43. J. Neurosci. 23:766–76 [Google Scholar]
  84. Lee HY, Xu Y, Huang Y, Ahn AH, Auburger GW. 84.  et al. 2004. The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway. Hum. Mol. Genet. 13:3161–70 [Google Scholar]
  85. Chen DH, Matsushita M, Rainier S, Meaney B, Tisch L. 85.  et al. 2005. Presence of alanine-to-valine substitutions in myofibrillogenesis regulator 1 in paroxysmal nonkinesigenic dyskinesia: confirmation in 2 kindreds. Arch. Neurol. 62:597–600 [Google Scholar]
  86. Friedman A, Zakrzewska-Pniewska B, Domitrz I, Lee HY, Ptacek L, Kwiecinski H. 86.  2009. Paroxysmal non-kinesigenic dyskinesia caused by the mutation of MR-1 in a large Polish kindred. Eur. Neurol. 61:39–41 [Google Scholar]
  87. Hempelmann A, Kumar S, Muralitharan S, Sander T. 87.  2006. Myofibrillogenesis regulator 1 gene (MR-1) mutation in an Omani family with paroxysmal nonkinesigenic dyskinesia. Neurosci. Lett. 402:118–20 [Google Scholar]
  88. Rainier S, Thomas D, Tokarz D, Ming L, Bui M. 88.  et al. 2004. Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis. Arch. Neurol. 61:1025–29 [Google Scholar]
  89. Yeh TH, Lin JJ, Lai SC, Wu-Chou YH, Chen AC. 89.  et al. 2012. Familial paroxysmal nonkinesigenic dyskinesia: clinical and genetic analysis of a Taiwanese family. J. Neurol. Sci. 323:80–84 [Google Scholar]
  90. Ghezzi D, Viscomi C, Ferlini A, Gualandi F, Mereghetti P. 90.  et al. 2009. Paroxysmal non-kinesigenic dyskinesia is caused by mutations of the MR-1 mitochondrial targeting sequence. Hum. Mol. Genet. 18:1058–64 [Google Scholar]
  91. Lee HY, Nakayama J, Xu Y, Fan X, Karouani M. 91.  et al. 2012. Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia. J. Clin. Investig. 122:507–18 [Google Scholar]
  92. Gundelfinger ED, Fejtova A. 92.  2011. Molecular organization and plasticity of the cytomatrix at the active zone. Curr. Opin. Neurobiol. 22:423–30 [Google Scholar]
  93. Kaeser PS. 93.  2011. Pushing synaptic vesicles over the RIM. Cell. Logist. 1:106–10 [Google Scholar]
  94. Kaeser PS, Deng L, Fan M, Südhof TC. 94.  2012. RIM genes differentially contribute to organizing presynaptic release sites. PNAS 109:11830–35 [Google Scholar]
  95. Nagao M, Fujita Y, Sugimura T, Kosuge T. 95.  1986. Methylglyoxal in beverages and foods: its mutagenicity and carcinogenicity. IARC Sci. Publ. 1986:283–91 [Google Scholar]
  96. Thornalley PJ. 96.  1990. The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem. J. 269:1–11 [Google Scholar]
  97. Thornalley PJ. 97.  1993. The glyoxalase system in health and disease. Mol. Aspects Med. 14:287–371 [Google Scholar]
  98. Thornalley PJ. 98.  1996. Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification—a role in pathogenesis and antiproliferative chemotherapy. Gen. Pharmacol. 27:565–73 [Google Scholar]
  99. Shen Y, Lee HY, Rawson J, Ojha S, Babbitt P. 99.  et al. 2011. Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability. Hum. Mol. Genet. 20:2322–32 [Google Scholar]
  100. Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W. 100.  et al. 2011. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat. Genet. 43:1252–55 [Google Scholar]
  101. Cloarec R, Bruneau N, Rudolf G, Massacrier A, Salmi M. 101.  et al. 2012. PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. Neurology 79:2097–103 [Google Scholar]
  102. Heron SE, Grinton BE, Kivity S, Afawi Z, Zuberi SM. 102.  et al. 2012. PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. Am. J. Hum. Genet. 90:152–60 [Google Scholar]
  103. Lee YC, Lee MJ, Yu HY, Chen C, Hsu CH. 103.  et al. 2012. PRRT2 mutations in paroxysmal kinesigenic dyskinesia with infantile convulsions in a Taiwanese cohort. PLOS ONE 7:e38543 [Google Scholar]
  104. Meneret A, Grabli D, Depienne C, Gaudebout C, Picard F. 104.  et al. 2012. PRRT2 mutations: a major cause of paroxysmal kinesigenic dyskinesia in the European population. Neurology 79:170–74 [Google Scholar]
  105. Okumura A, Shimojima K, Kubota T, Abe S, Yamashita S. 105.  et al. 2013. PRRT2 mutation in Japanese children with benign infantile epilepsy. Brain Dev. 35:641–46 [Google Scholar]
  106. Schubert J, Paravidino R, Becker F, Berger A, Bebek N. 106.  et al. 2012. PRRT2 mutations are the major cause of benign familial infantile seizures. Hum. Mutat. 33:1439–43 [Google Scholar]
  107. Wang JL, Cao L, Li XH, Hu ZM, Li JD. 107.  et al. 2011. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain 134:3493–501 [Google Scholar]
  108. Gardiner AR, Bhatia KP, Stamelou M, Dale RC, Kurian MA. 108.  et al. 2012. PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. Neurology 79:2115–21 [Google Scholar]
  109. Heron SE, Dibbens LM. 109.  2013. Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy. J. Med. Genet. 50:133–39 [Google Scholar]
  110. Meneret A, Gaudebout C, Riant F, Vidailhet M, Depienne C, Roze E. 110.  2013. PRRT2 mutations and paroxysmal disorders. Eur. J. Neurol. 20:872–78 [Google Scholar]
  111. Hedera P, Xiao J, Puschmann A, Momcilovic D, Wu SW, LeDoux MS. 111.  2012. Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia. BMC Neurol. 12:93 [Google Scholar]
  112. Groffen AJ, Klapwijk T, van Rootselaar AF, Groen JL, Tijssen MA. 112.  2013. Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia. J. Neurol. 260:93–99 [Google Scholar]
  113. Riant F, Roze E, Barbance C, Meneret A, Guyant-Marechal L. 113.  et al. 2012. PRRT2 mutations cause hemiplegic migraine. Neurology 79:2122–24 [Google Scholar]
  114. van Vliet R, Breedveld G, de Rijk-van Andel J, Brilstra E, Verbeek N. 114.  et al. 2012. PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions. Neurology 79:777–84 [Google Scholar]
  115. Stojilkovic SS. 115.  2005. Ca2+-regulated exocytosis and SNARE function. Trends Endocrinol. Metab. 16:81–83 [Google Scholar]
  116. Zhao N, Hashida H, Takahashi N, Sakaki Y. 116.  1994. Cloning and sequence analysis of the human SNAP25 cDNA. Gene 145:313–14 [Google Scholar]
  117. Hu K, Carroll J, Fedorovich S, Rickman C, Sukhodub A, Davletov B. 117.  2002. Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion. Nature 415:646–50 [Google Scholar]
  118. Sorensen JB, Matti U, Wei SH, Nehring RB, Voets T. 118.  et al. 2002. The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis. PNAS 99:1627–32 [Google Scholar]
  119. Chin LS, Li L, Ferreira A, Kosik KS, Greengard P. 119.  1995. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I–deficient mice. PNAS 92:9230–34 [Google Scholar]
  120. Giovedi S, Vaccaro P, Valtorta F, Darchen F, Greengard P. 120.  et al. 2004. Synapsin is a novel Rab3 effector protein on small synaptic vesicles. I. Identification and characterization of the synapsin I–Rab3 interactions in vitro and in intact nerve terminals. J. Biol. Chem. 279:43760–68 [Google Scholar]
  121. Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS. 121.  et al. 1995. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I–deficient mice. PNAS 92:9235–39 [Google Scholar]
  122. Dale RC, Grattan-Smith P, Fung VS, Peters GB. 122.  2011. Infantile convulsions and paroxysmal kinesigenic dyskinesia with 16p11.2 microdeletion. Neurology 77:1401–2 [Google Scholar]
  123. Dale RC, Grattan-Smith P, Nicholson M, Peters GB. 123.  2012. Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study. Dev. Med. Child Neurol. 54:618–23 [Google Scholar]
  124. Lipton J, Rivkin MJ. 124.  2009. 16p11.2-related paroxysmal kinesigenic dyskinesia and dopa-responsive parkinsonism in a child. Neurology 73:479–80 [Google Scholar]
  125. Weber A, Kohler A, Hahn A, Neubauer B, Muller U. 125.  2013. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome. Neurogenetics 14:251–53 [Google Scholar]
  126. Mullen SA, Suls A, De Jonghe P, Berkovic SF, Scheffer IE. 126.  2010. Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. Neurology 75:432–40 [Google Scholar]
  127. Suls A, Dedeken P, Goffin K, Van Esch H, Dupont P. 127.  et al. 2008. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1. Brain 131:1831–44 [Google Scholar]
  128. Weber YG, Storch A, Wuttke TV, Brockmann K, Kempfle J. 128.  et al. 2008. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J. Clin. Investig. 118:2157–68 [Google Scholar]
  129. Auburger G, Ratzlaff T, Lunkes A, Nelles HW, Leube B. 129.  et al. 1996. A gene for autosomal dominant paroxysmal choreoathetosis/spasticity (CSE) maps to the vicinity of a potassium channel gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. Genomics 31:90–94 [Google Scholar]
  130. Weber YG, Kamm C, Suls A, Kempfle J, Kotschet K. 130.  et al. 2011. Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect. Neurology 77:959–64 [Google Scholar]
  131. Agus DB, Gambhir SS, Pardridge WM, Spielholz C, Baselga J. 131.  et al. 1997. Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters. J. Clin. Investig. 100:2842–48 [Google Scholar]
  132. Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R. 132.  et al. 2008. Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell 132:1039–48 [Google Scholar]
  133. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI. 133.  1991. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N. Engl. J. Med. 325:703–9 [Google Scholar]
  134. Leen WG, Klepper J, Verbeek MM, Leferink M, Hofste T. 134.  et al. 2010. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 133:655–70 [Google Scholar]
  135. Pascual JM, Wang D, Lecumberri B, Yang H, Mao X. 135.  et al. 2004. GLUT1 deficiency and other glucose transporter diseases. Eur. J. Endocrinol. 150:627–33 [Google Scholar]
  136. Brockmann K. 136.  2009. The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev. 31:545–52 [Google Scholar]
  137. De Giorgis V, Veggiotti P. 137.  2013. GLUT1 deficiency syndrome 2013: current state of the art. Seizure 22:803–11 [Google Scholar]
  138. Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA. 138.  2014. GLUT1 deficiency syndrome into adulthood: a follow-up study. J. Neurol. 261:589–99 [Google Scholar]
  139. Ptáček LJ. 139.  2015. Episodic disorders: channelopathies and beyond. Annu. Rev. Physiol. 77:475–79 [Google Scholar]
  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error