2001 年度実績報告書

てんかんおよび熱性けいれんの遺伝子解析

研究課題

研究課題/領域番号	12307019
研究機関	弘前大学
研究代表者	兼子直弘前大学, 医学部, 教授 (40106852)
研究分担者	満留昭久福岡大学, 医学部, 教授 (30038749) 佐野輝愛媛大学, 医学部, 助教授 (30178800) 辻省次新潟大学, 脳研究所, 教授 (70150612) 伊藤正利滋賀県立小児保健医療センター, 副部長(研究職) (90135567) 山川和弘理化学研究所, 脳科学総合センター, チームリーダー (30241235)
キーワード	GEFS+ / SCN1A / SCN2A / GABA receptor / Chorein / Juvenile myoclonic epilepsy / BFNC / BFNC
研究概要	1.熱性けいれんプラス(generalized epilepsy febrile seizure plus : GEFS+)関連世界に先駆け、GEFS+の責任遺伝子の一つとしてNa+イオンチャネルSCN2Aを同定し、同時にSCN1Aの変異も複数発見し報告した。一方、変異遺伝子と臨床類型の研究から、GEFS+症例には部分発作を伴うことを見いだし、GEFS+はAutosomal dominant epilepsy with febrile seizures plusと命名すべきことを指摘した。 2.てんかん発作を伴うchorea acanthocytosisの責任遺伝子である新奇蛋白choreinを同定した。 3.Severe myoclonic epilepsy in infancy(SMEI)の責任遺伝子として、Na+イオンチャネルSCN1Aにおける複数の変異を同定し、SMEIにはGABA-A受容体のγ2サブユニットの変異も関連することを発見し、投稿中である。 4.Juvenile myoclonic epilepsyの強力な候補遺伝子を発見し、投稿中である。 5.良性家族性新生児けいれんの(BFNC)責任遺伝子であるKCNQ2,3が発作を起こすが、その発作発現と消失に関わる分子病態を明らかにした。 6.以上のような研究の進展に伴い、2002年度は欠神発作などの頻度の高いてんかん類型の遺伝子座位を決定する目的で、ゲノムワイドスキャンを行う予定である。

研究成果

(47件)

すべてその他

すべて文献書誌 (47件)

[文献書誌] M Okada, et al.: "Impaired M-current and neuronal excitability"Epilepsia. (In press). (2002)
[文献書誌] M Ito, et al.: "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na^+)-channel α1 subunit gene, SCN1A"Epilepsy Research. 48(In press). (2002)
[文献書誌] T Takahashi, et al.: "Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a T666M mutation in the CACNA1A gene"Journal of Neurology Neurosurgery and Psychitry. (In press). (2002)
[文献書誌] N Matsushima, et al.: "Mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α 4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocytes"Epilepsy Research. 48. 15-23 (2002)
[文献書誌] M Ito, et al.: "Low-dose ACTH therapy for West syndrome : Initial effects and long-term outcome"Neurology. 58(1-2). 110-114 (2002)
[文献書誌] M Ito: "Extremely low-dose ACTH therapy for West syndrome in Japan"Brain & Development. 23. 635-641 (2001)
[文献書誌] T Murakami, et al.: "Determination of effects of antiepileptio drugs on SNARs-mediated hippocampal monoamine release using in vivo microdialysis"British Journal of Pharmacology. 134. 507-520 (2001)
[文献書誌] I Yoshimura, et al.: "Long-term observations of two siblings with Lafora disease treated with zonisamide"Epilepsy Research. 46. 283-287 (2001)
[文献書誌] S Ueno, et al.: "The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis"Nature Genetics. 28(7). 121-122 (2001)
[文献書誌] Y Kawata, et al.: "Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca^<2+>-and K^+ evoked serotonin releases"British Journal of Pharmacology. 133. 557-567 (2001)
[文献書誌] K Wada, et al.: "Sociomedical aspects of epileptic patients : Their employment and marital status"Psychiatry and Clinical Neurosciences. 55(2). 141-146 (2001)
[文献書誌] M Okada, et al.: "Adenosin receptor subtypes modulate two major functional pathways for hippocampal serotonin release"Journal of Neuroscience. 21(2). 628-640 (2001)
[文献書誌] Y Sugimoto, et al.: "T-STAR gene : fine mapping in the candidate region for childhood absence epilepsy on 8q24 and mutational analysis in patients"Epilepsy Research. 46. 139-144 (2001)
[文献書誌] T Suzuki, et al.: "A novel gene in the chromosomal region for juvenile myoclonic epilepsy on 6q12 encodes a brain-specific lysosomal membrane protein"Biochemical and Biophysical Research Communications. 288. 626-636 (2001)
[文献書誌] T Sugawara, et al.: "Na_v1.1 mutations cause febrile seizures associated with afebrile partial seizures"Neurology. 57. 703-705 (2001)
[文献書誌] T Sugawara, et al.: "A missense mutation of the Na^+ channel α_<II> subunit gene Na_v1.2 in a patients with febrile and afebrile seizures causes channel dysfunction"P NATL ACAD SCI USA. 98(11). 6384-6389 (2001)
[文献書誌] S Ganesh, et al.: "Regional and development expression of Epm2a gene and its evolutionary conservation"Biochemical and Biophysical Research Communications. 283. 1046-1053 (2001)
[文献書誌] S Ganesh, et al.: "Mutation screening for Japanese Lafore's disease patients : Identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene"Molecular and Cellular Probes. 15. 281-289 (2001)
[文献書誌] H Oguni, et al.: "Study on early-onset benign occipital seizure susceptibility syndrome"Pediatric Neurology. 25(4). 312-318 (2001)
[文献書誌] E Tachikawa, et al.: "Acquired epileptiform opercular syndrome : a case report and results single photon emission computed tomography and computer-assisted electroencephalographic analysis"Brain & Development. 23. 246-250 (2001)
[文献書誌] H Oguni, et al.: "Severe myoclonic epilepsy in infants-a review based on the Tokyo Women's Medical University series of 84 cases"Brain & Development. 23. 736-748 (2001)
[文献書誌] H Oguni, et al.: "Myoclonic-astatic epilepsy of early childhood-clinical and EEG analysis of myoclonic-astatic seizures, and discussions on the nosology of the syndrome"Brain & Development. 23. 757-764 (2001)
[文献書誌] S Shirakawa, et al.: "A study of the effect of color photostimulation from a cathode-ray tube(CRT) display on photosensitive patients : The effect of alternating red-cyan flicker stimulation"Epilepsia. 42(7). 922-929 (2001)
[文献書誌] M Funatsuka, et al.: "Study on photo-pattern sensitivity in patients with electronic screen gome-induced seizures(ESGS) : Effects of spatial resolution, brightness, and pattern movement"Epilepsia. 42(9). 1185-1197 (2001)
[文献書誌] M Ueno, et al.: "Neurophysiological study of secondary synchronous occipito-frontopolar spikes in childhood"Clinical Neurophysiology. 112. 2106-2112 (2001)
[文献書誌] Y Goto: "Clinical and molecular studies of mitochondrialdisease"J Inherit Metab Dis. 24. 181-188 (2001)
[文献書誌] N Adachi, et al.: "Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis"J Neuropsychitry Clin Neurosci. 13(2). 258-260 (2001)
[文献書誌] Y Goto, et al.: "Mitochodrial DNA deletion and duplication in human disease and mouse model"Acta Myologica. 20. 110-114 (2001)
[文献書誌] T Ohura, et al.: "Neonatal presentation of adult-onset type II citrullinemia"Hum Genet. 108. 87-90 (2001)
[文献書誌] O Sakamoto, et al.: "A novel intronic mutation of the TAZ (G4.5) gene in a patient with Barth syndrome : creation of a 5'splice donor site with variant GC consensus and elongation of the upstream exon"Hum Genet. 109. 559-563 (2001)
[文献書誌] K Haginoya, et al.: "Mechanism of tonic spasms in West syndrome viewed from ictal SPECT findings"Brain & Development. 23. 496-501 (2001)
[文献書誌] Y Aoki, et al.: "A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease"Neuroscience Letters. 312. 71-74 (2001)
[文献書誌] H Date, et al.: "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene"Nature Genetics. 29. 184-188 (2001)
[文献書誌] A Okumura, et al.: "Five-year follow-up of patients with partial epilepsies in infancy"Pediatric Neurology. 24(4). 290-296 (2001)
[文献書誌] K Watanabe, et al.: "Symptomatology of infantile spasms"Brain & Development. 23. 453-466 (2001)
[文献書誌] A Okumura, et al.: "Clinico-electrical evolution in per-hypsarrythmic stage : toward prediction and prevention of West syndrome"Brain & Development. 23. 482-487 (2001)
[文献書誌] A Okumura, et al.: "The timing of brain insults preterm infants who later developed West syndrome"Neuropediatrics. 32. 245-249 (2001)
[文献書誌] H Akiyoshi, et al: "A novel SSCP varient (c.828G>A) within the M2 domain of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit gene, CHRNA4"Human Genetics. 16(5)(online). (2000)
[文献書誌] 兼子直, 他: "てんかん・熱性けいれんの遺伝子解析"脳21. 4(3). 31-35 (2001)
[文献書誌] 兼子直: "てんかん遺伝子研究の現状と将来展望"実験医学. 19(17). 2289-2296 (2001)
[文献書誌] 兼子直, 他: "てんかんの分子病態"精神神経学雑誌. 103(9). 712-717 (2001)
[文献書誌] 兼子直, 他: "てんかんの分子医学"現代医療. 33(11). 2755-2760 (2001)
[文献書誌] 佐野輝: "遺伝性てんかん"最新精神医学. 6(6). 553-558 (2001)
[文献書誌] 佐野輝: "ミオクローヌスてんかんの分子遺伝学"分子精神医学. 1(4). 351-357 (2001)
[文献書誌] 丸山幸一, 他: "欠神発作を主症状とした前頭葉てんかんの1例"脳と発達. 34(1). 72-76 (2002)
[文献書誌] 奥村彰久, 他: "脳波異常を伴う熱性けいれんの取り扱いに関するアンケート調査"小児科臨床. 54(10). 1877-1882 (2001)
[文献書誌] 渡辺一功: "てんかん症候群分類における最近の進歩"小児科. 42(11). 1754-1763 (2001)

2001 年度 実績報告書

てんかんおよび熱性けいれんの遺伝子解析

研究代表者

兼子 直 弘前大学, 医学部, 教授 (40106852)

研究成果

[文献書誌] M Okada, et al.: "Impaired M-current and neuronal excitability"Epilepsia. (In press). (2002)

[文献書誌] M Ito, et al.: "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na^+)-channel α1 subunit gene, SCN1A"Epilepsy Research. 48(In press). (2002)

[文献書誌] T Takahashi, et al.: "Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a T666M mutation in the CACNA1A gene"Journal of Neurology Neurosurgery and Psychitry. (In press). (2002)

[文献書誌] N Matsushima, et al.: "Mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α 4 subunit associated with frontal lobe epilepsy causes faster desensitization of the rat receptor expressed in oocytes"Epilepsy Research. 48. 15-23 (2002)

[文献書誌] M Ito, et al.: "Low-dose ACTH therapy for West syndrome : Initial effects and long-term outcome"Neurology. 58(1-2). 110-114 (2002)

[文献書誌] M Ito: "Extremely low-dose ACTH therapy for West syndrome in Japan"Brain & Development. 23. 635-641 (2001)

[文献書誌] T Murakami, et al.: "Determination of effects of antiepileptio drugs on SNARs-mediated hippocampal monoamine release using in vivo microdialysis"British Journal of Pharmacology. 134. 507-520 (2001)

[文献書誌] I Yoshimura, et al.: "Long-term observations of two siblings with Lafora disease treated with zonisamide"Epilepsy Research. 46. 283-287 (2001)

[文献書誌] S Ueno, et al.: "The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis"Nature Genetics. 28(7). 121-122 (2001)

[文献書誌] Y Kawata, et al.: "Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca^<2+>-and K^+ evoked serotonin releases"British Journal of Pharmacology. 133. 557-567 (2001)

[文献書誌] K Wada, et al.: "Sociomedical aspects of epileptic patients : Their employment and marital status"Psychiatry and Clinical Neurosciences. 55(2). 141-146 (2001)

[文献書誌] M Okada, et al.: "Adenosin receptor subtypes modulate two major functional pathways for hippocampal serotonin release"Journal of Neuroscience. 21(2). 628-640 (2001)

[文献書誌] Y Sugimoto, et al.: "T-STAR gene : fine mapping in the candidate region for childhood absence epilepsy on 8q24 and mutational analysis in patients"Epilepsy Research. 46. 139-144 (2001)

[文献書誌] T Suzuki, et al.: "A novel gene in the chromosomal region for juvenile myoclonic epilepsy on 6q12 encodes a brain-specific lysosomal membrane protein"Biochemical and Biophysical Research Communications. 288. 626-636 (2001)

[文献書誌] T Sugawara, et al.: "Na_v1.1 mutations cause febrile seizures associated with afebrile partial seizures"Neurology. 57. 703-705 (2001)

[文献書誌] T Sugawara, et al.: "A missense mutation of the Na^+ channel α_<II> subunit gene Na_v1.2 in a patients with febrile and afebrile seizures causes channel dysfunction"P NATL ACAD SCI USA. 98(11). 6384-6389 (2001)

[文献書誌] S Ganesh, et al.: "Regional and development expression of Epm2a gene and its evolutionary conservation"Biochemical and Biophysical Research Communications. 283. 1046-1053 (2001)

[文献書誌] S Ganesh, et al.: "Mutation screening for Japanese Lafore's disease patients : Identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene"Molecular and Cellular Probes. 15. 281-289 (2001)

[文献書誌] H Oguni, et al.: "Study on early-onset benign occipital seizure susceptibility syndrome"Pediatric Neurology. 25(4). 312-318 (2001)

[文献書誌] E Tachikawa, et al.: "Acquired epileptiform opercular syndrome : a case report and results single photon emission computed tomography and computer-assisted electroencephalographic analysis"Brain & Development. 23. 246-250 (2001)

[文献書誌] H Oguni, et al.: "Severe myoclonic epilepsy in infants-a review based on the Tokyo Women's Medical University series of 84 cases"Brain & Development. 23. 736-748 (2001)

[文献書誌] H Oguni, et al.: "Myoclonic-astatic epilepsy of early childhood-clinical and EEG analysis of myoclonic-astatic seizures, and discussions on the nosology of the syndrome"Brain & Development. 23. 757-764 (2001)

[文献書誌] S Shirakawa, et al.: "A study of the effect of color photostimulation from a cathode-ray tube(CRT) display on photosensitive patients : The effect of alternating red-cyan flicker stimulation"Epilepsia. 42(7). 922-929 (2001)

[文献書誌] M Funatsuka, et al.: "Study on photo-pattern sensitivity in patients with electronic screen gome-induced seizures(ESGS) : Effects of spatial resolution, brightness, and pattern movement"Epilepsia. 42(9). 1185-1197 (2001)

[文献書誌] M Ueno, et al.: "Neurophysiological study of secondary synchronous occipito-frontopolar spikes in childhood"Clinical Neurophysiology. 112. 2106-2112 (2001)

[文献書誌] Y Goto: "Clinical and molecular studies of mitochondrialdisease"J Inherit Metab Dis. 24. 181-188 (2001)

[文献書誌] N Adachi, et al.: "Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis"J Neuropsychitry Clin Neurosci. 13(2). 258-260 (2001)

[文献書誌] Y Goto, et al.: "Mitochodrial DNA deletion and duplication in human disease and mouse model"Acta Myologica. 20. 110-114 (2001)

[文献書誌] T Ohura, et al.: "Neonatal presentation of adult-onset type II citrullinemia"Hum Genet. 108. 87-90 (2001)

[文献書誌] O Sakamoto, et al.: "A novel intronic mutation of the TAZ (G4.5) gene in a patient with Barth syndrome : creation of a 5'splice donor site with variant GC consensus and elongation of the upstream exon"Hum Genet. 109. 559-563 (2001)

[文献書誌] K Haginoya, et al.: "Mechanism of tonic spasms in West syndrome viewed from ictal SPECT findings"Brain & Development. 23. 496-501 (2001)

[文献書誌] Y Aoki, et al.: "A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease"Neuroscience Letters. 312. 71-74 (2001)

[文献書誌] H Date, et al.: "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene"Nature Genetics. 29. 184-188 (2001)

[文献書誌] A Okumura, et al.: "Five-year follow-up of patients with partial epilepsies in infancy"Pediatric Neurology. 24(4). 290-296 (2001)

[文献書誌] K Watanabe, et al.: "Symptomatology of infantile spasms"Brain & Development. 23. 453-466 (2001)

[文献書誌] A Okumura, et al.: "Clinico-electrical evolution in per-hypsarrythmic stage : toward prediction and prevention of West syndrome"Brain & Development. 23. 482-487 (2001)

[文献書誌] A Okumura, et al.: "The timing of brain insults preterm infants who later developed West syndrome"Neuropediatrics. 32. 245-249 (2001)

[文献書誌] H Akiyoshi, et al: "A novel SSCP varient (c.828G>A) within the M2 domain of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit gene, CHRNA4"Human Genetics. 16(5)(online). (2000)

[文献書誌] 兼子 直, 他: "てんかん・熱性けいれんの遺伝子解析"脳21. 4(3). 31-35 (2001)

[文献書誌] 兼子 直: "てんかん遺伝子研究の現状と将来展望"実験医学. 19(17). 2289-2296 (2001)

[文献書誌] 兼子 直, 他: "てんかんの分子病態"精神神経学雑誌. 103(9). 712-717 (2001)

[文献書誌] 兼子 直, 他: "てんかんの分子医学"現代医療. 33(11). 2755-2760 (2001)

[文献書誌] 佐野 輝: "遺伝性てんかん"最新精神医学. 6(6). 553-558 (2001)

[文献書誌] 佐野 輝: "ミオクローヌスてんかんの分子遺伝学"分子精神医学. 1(4). 351-357 (2001)

[文献書誌] 丸山幸一, 他: "欠神発作を主症状とした前頭葉てんかんの1例"脳と発達. 34(1). 72-76 (2002)

[文献書誌] 奥村彰久, 他: "脳波異常を伴う熱性けいれんの取り扱いに関するアンケート調査"小児科臨床. 54(10). 1877-1882 (2001)

[文献書誌] 渡辺一功: "てんかん症候群分類における最近の進歩"小児科. 42(11). 1754-1763 (2001)

2001 年度実績報告書

兼子直弘前大学, 医学部, 教授 (40106852)

[文献書誌] 兼子直, 他: "てんかん・熱性けいれんの遺伝子解析"脳21. 4(3). 31-35 (2001)

[文献書誌] 兼子直: "てんかん遺伝子研究の現状と将来展望"実験医学. 19(17). 2289-2296 (2001)

[文献書誌] 兼子直, 他: "てんかんの分子病態"精神神経学雑誌. 103(9). 712-717 (2001)

[文献書誌] 兼子直, 他: "てんかんの分子医学"現代医療. 33(11). 2755-2760 (2001)

[文献書誌] 佐野輝: "遺伝性てんかん"最新精神医学. 6(6). 553-558 (2001)

[文献書誌] 佐野輝: "ミオクローヌスてんかんの分子遺伝学"分子精神医学. 1(4). 351-357 (2001)