1998 Fiscal Year Annual Research Report

てんかんおよび熱性けいれんの遺伝(子)解析

Research Project

Project/Area Number	09470206
Research Institution	Hirosaki University
Principal Investigator	兼子直弘前大学, 医学部, 教授 (40106852)
Co-Investigator(Kenkyū-buntansha)	大沼悌一国立療養所, 犀潟病院, 院長 (30003536) 満留昭久福岡大学, 医学部, 教授 (30038749) 佐野輝愛媛大学, 医学部附属病院, 助教授 (30178800) 小国弘量東京女子医科大学, 助教授 (60130241) 辻省次新潟大学, 脳研究所, 教授 (70150612)
Keywords	てんかん / 熱性けいれん / 遺伝子 / 家系調査 / 連鎖解析
Research Abstract	本年度の主な成果として、 1) アジア人における初のautosomal dominant nocturnal frontal lobe epilepsy(ADNFLE)家系を発見し、この家系の特徴を解析し、投稿した。また、ADNFLEの遺伝子座位を特定し、新たなpoint mutationとして、CHRNA4遺伝子のexon 5におけるC752Tを発見し、これも投稿中である。 2) Benign adult familial myoclonic epilepsyの遺伝子座位は第8番染色体長腕上に存在することを見いだし現在positional cloning中である。本てんかんの遺伝子の座位については現在投稿中である。 3) Juvenile myoclonic epilepsyの遺伝子座位は第6番染色体上あるいは第15番染色体上に存在すると報告されているが、日本人の家系を用いて検討した結果、第6番染色体上に存在し、その位置は6p21.2-11であるとの結果が得られ、これも投稿中である。 4) てんかんの病態にはK,Ca,Naイオンチャネル異常が深く関与しているものと考えられ、抗てんかん薬とイオンチャネルとの関連を追及しつつあり、特に、Ca^<2+>とK^+の神経伝達物質遊離に対する効果、組織内イオン濃度変化と神経細胞興奮、adenosine受容体サブタイプと神経伝達との関連を解析し、この分野でも大きな成果を上げている。 5) 脳内に特異的に存在するKイオンチャネルを発見し、現在、これとてんかんが関連するか否か検討中である 6) その他のてんかん類型、例えば、benign familial infantile convulsion、febrile convulsion、severemyoclonic epilepsy in infancyの遺伝子座位を連鎖解析中である。また、informativeな家系からのサンプル採集を進めており、近日中により多くの成果が期待される。

Research Products

(56 results)

All Other

All Publications (56 results)

[Publications] S Tsuji,: "Unstable expansion of triplet repeats as a new mechanism for neurodegenerative diseases" Internal Medicine. 36. 3-8 (1997)
[Publications] S Igarashi,: "Atypical clinical presentations of X-linked spinal and bulbar muscular atrophy in patients with mild CAG expansions in androgen receptor gene" Eur Neurol. 38. 310-312 (1997)
[Publications] T Ikeuchi,: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9" Ann Neurol. 41. 432-437 (1997)
[Publications] YX Zhou,: "Machado-Joseph disease in four Chinese pedigrees : Molecular analysis of 15 patients including two juvenile cases and clinical correlations" Neurology. 48. 482-485 (1997)
[Publications] M Oyake,: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA. Strong conservation of a polymorphic CAG repeat in the murine gene" Genomics. 40. 205-207 (1997)
[Publications] K Muraki,: "Severe lactic acidosis and neonatal death Pearson syndrome" J Inher Metab Dis. 20. 43-48 (1997)
[Publications] A Seki,: "Mitochondrial encephalomyopathy with 15915 mutation : case report" Pediatr Neurol. 17. 161-164 (1997)
[Publications] M Ozawa,: "Myoclonus epilepsy associated with ragged-red fibers : A G-TO-A mutation at nucleotide pair 8363 in mitochondrial tRNA^<Lys> in two families" Muscle Nerve. 20. 271-278 (1997)
[Publications] M Okada,: "Effects of carbamazepine on hippocampal serotonergic system." Epilepsy Res. 31・3. 187-198 (1998)
[Publications] M Okada,: "Interaction between Ca^<2+>,K^+ carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode." Brit J Pharmacol. 124. 1277-1285 (1998)
[Publications] S Kaneko: "Pregancy and quality of life in women with epilepsy." Clin Ther. 20 Suppl.A. A30-A47 (1998)
[Publications] M Okada,: "Effects of antiepileptic drugs on K^+-induced glutamate release spreading depression in the hippocampus determined with an in vivo microdyalysis glutamate biosensor(MGB)." Epilepsia. 39 Suppl.5. 56 (1998)
[Publications] K Wada: "Occupational and marital status of patients with epilepsy." Epilepsia. 39 Suppl.5. 66-67 (1998)
[Publications] M Okada,: "Pharmacological interactions between magnesium ion and adenosine on monoaminergic system in the central nervous system." Magnesium Res. 11. 289-305 (1998)
[Publications] 奥村彰久,: "ほぼ同時に発症した「軽症下痢に伴うけいれん」の一卵性双生児例" 脳と発達. 31. 59-62 (1999)
[Publications] 奥村彰久,: "「軽症胃腸炎に伴うけいれん」の臨床像" 小児科臨床. 52. 51-55 (1999)
[Publications] T Sato,: "Transgenic mice harboring a full-length human mutant DRPLA gene exhibit agedependent intergenerational and somatic instabilities of CAG repeats comparable to those in DRPLA patients." Hum Mol Genet. 8・1. 99-106 (1999)
[Publications] 前澤真理子,: "神経性食欲不振症とcontra-coup injury-治療経過と画像診断-" 脳と発達. 31・1. 88-89 (1999)
[Publications] J Ono,: "Ring chromosome 14 complicated with complex partial seizures and hypoplastic corpus callosum." Pediatr Neurol. 20・1. 70-72 (1999)
[Publications] M Okada,: "Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin." Eur J Neurosci. 11. 1-9 (1999)
[Publications] S Kaneko: "Congenital malformations due to antiepileptic drugs." Epilepsy Res. 32. in press (1999)
[Publications] 宮本百合子,: "部分発作とみなされるてんかん発作症状を持つ良性成人型家族性ミオクローヌスてんかん(Benign adult familial myoclonus epilepsy(BAFME)の1家系" てんかん研究. 17・1(印刷中). (1999)
[Publications] S Tobimatsu,: "Chromative sensitive epilepsy-A variant of photosensitive epilepsy." Ann Neurol. (accepted). (1999)
[Publications] H Utsunomiya,: "Development of the temporal lobe in infants and children ; Analysis by MR-based volumetry." Amer J Neuroradiol. (accepted). (1999)
[Publications] 満留昭久,: "テレビアニメ「ポケットモンスター」視聴により誘発された光感受性発作に関する臨床的・脳波学的検討" 厚生科学特別研究「光感受性発作に関する臨床研究」報告書. 71-76 (1998)
[Publications] 飛松省三,: "視覚誘発電位、脳波、脳磁図を用いたポケモン発作の発症機序に関する研究" 厚生科学特別研究「光感受性発作に関する臨床研究」報告書. 113-121 (1998)
[Publications] 大府正治,: "中心・側頭部に棘波を有する良性小児部分てんかん(BECT)における高振幅SEP : 睡眠・覚醒による変化" 脳波と筋電図. 26. 285-291 (1998)
[Publications] 大府正治,: "インフルエンザ脳症後、驚愕てんかんを呈した2例" 臨床脳波. 40. 682-686 (1998)
[Publications] 大府正治,: "乳児重症ミオクロニーてんかん(SMEI)における高振幅体性感覚誘発電位の経時的変化についての研究-周辺群および熱性痙攣との比較-" てんかん治療研究振興財団研究年報. 10. 133-137 (1998)
[Publications] S Igarashi,: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet. 18. 111-117 (1998)
[Publications] M Saito,: "Refinement of the gene locus for autosomal recessive juvenile parkinsonism(AR-JP)on chromosome 6q25.2-27 and identification of markers exhibiting linkage disequilibrium." J Hum Genet. 43. 22-31 (1998)
[Publications] E Sidransky,: "A triplet repeat on 17q accounts for most expansions detected by the repeat expansion detection technique." Amer J Hum Genet. 62・6. 1548-1551 (1998)
[Publications] S Tsuji: "Dentatorubral-pallidoluysian atrophy(DRPLA)." Analysis of Triplet Repeat Disorders,edited by Rubinsztein,D.C.and Hayden,M.R.BIOS Scientific Publishers,Oxford.209-218 (1998)
[Publications] 前澤真理子,: "ローランド棘波とTVモニターにより誘発されたけいれん" 脳波と筋電図. 26・3. 262-263 (1998)
[Publications] 前澤真理子,: "環境ホルモン(外因性内分泌攪乱物質)と小児の診療" 産婦人科の世界. 51・1. 65-69 (1998)
[Publications] A Honda,: "Isolated lissencephaly sequence with balanced chromosome translocation involving 17p13.3." Brain Dev. 20. 190-192 (1998)
[Publications] H Kurahashi,: "Molecular cloning of the chromosomal breakpoint in the LIS1 gene of a patient with isolated lissencephaly and balanced t(8 ; 17)." Hum Genet. 103. 189-192 (1998)
[Publications] M Sakamoto,: "Alteration of the LIS1 gene in Japanese patients with isolated lissencephaly sequence or Miller-Dieker syndrome." Hum Genet. 103. 586-589 (1998)
[Publications] H Takano,: "Close associations between prevalence of dominantly irherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian-populations." Am J Hum Genet. 63・4. 1060-1066 (1998)
[Publications] M Okada,: "Effects of Ca^<2+> channel antagonists on striatal dopamine and DOPA release,studies by in vivo microdialysis." Brit J Pharmacol. 123. 805-814 (1998)
[Publications] CD Ferrie,: "Early onset benign occipital seizure susceptibility syndrome" Epilepsia. 38. 285-293 (1997)
[Publications] K Aso,: "Frontal lobe epilepsy of childhood onset" Epilepsia. 38 Suppl.6. 40-41 (1997)
[Publications] T Ohoki,: "Severe myoclonic epilepsy in infancy evolution of seizures" Seizure. 6. 219-224 (1997)
[Publications] K Wada,: "Prognosis and clinical features of intractable epilepsy : A prospective study" Psychiat Clin Neurosciences. 51. 233-235 (1997)
[Publications] 満留昭久,: "日本人良性新生児けいれん(BFNC)家系でのNicotinic acethylcholine recept or α4 subunit(CHRNA-4)の変異の検索" てんかん治療研究振興財団研究年報. 9. 152-160 (1997)
[Publications] M Ozawa,: "Single muscle fiber analysis in patients with 3243 mutation in mitochondrial DNA : Comparision with the phenotype and the proportion of mutant genome." J Neurol Sci. 159. 170-175 (1998)
[Publications] M Makino,: "Confirmation that a T-to-C mutation at 9176 in mitochondrial DNA is an additional candidate mutation for Leigh's syndrome." Neuromuscul Disord. 8. 149-151 (1998)
[Publications] T Kuroiwa,: "Mitochondrial encephalomyopathy showing prominent microvacuolation and necrosis of intestinal smooth muscle cells : A case diagnosed by rectal biopsy." Acta Neuropathol. 96. 86-90 (1998)
[Publications] S Nishizuka,: "Tissue-specific involvement of multiple mitochondrial DNA deletions in familial mitochondrial myopathy." Biochem Biophys Res Commun. 247. 24-27 (1998)
[Publications] K Watanabe,: "West syndrome : etiological and prognostic aspects." Brain Dev. 20・1. 1-8 (1998)
[Publications] 渡辺一功,: "乳幼児期、児童期のてんかん" 臨床精神医学講座9 てんかん、中山書店、東京. 9. 254-264 (1998)
[Publications] 渡辺一功,: "脳の発達とてんかんの病態" 神経研究の進歩. 42. 954-961 (1998)
[Publications] 奥村彰久,: "早産児に発症したWest症候群-新生児期における脳波所見の経時的変化-" 臨床脳波. 40. 700-704 (1998)
[Publications] A Okumura,: "Evolutional changes and outcome of West syndrome : correlation with magnatic resonance imaging findings." Epilepsia. 39 Suppl.5. 46-49 (1998)
[Publications] Yan Ping Lin,: "Benign myoclonic epilepsy in infants : Video-EEG features and log-term follow-up." Neuropediatr. 29. 268-271 (1998)
[Publications] S Hirose,: "Valproate therapy does not deplete carnitine levels in otherwise healthy children." Pediatrics. 101・5. 1-5 (1998)

1998 Fiscal Year Annual Research Report

てんかんおよび熱性けいれんの遺伝(子)解析

Principal Investigator

兼子 直 弘前大学, 医学部, 教授 (40106852)

Research Products

[Publications] S Tsuji,: "Unstable expansion of triplet repeats as a new mechanism for neurodegenerative diseases" Internal Medicine. 36. 3-8 (1997)

[Publications] S Igarashi,: "Atypical clinical presentations of X-linked spinal and bulbar muscular atrophy in patients with mild CAG expansions in androgen receptor gene" Eur Neurol. 38. 310-312 (1997)

[Publications] T Ikeuchi,: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9" Ann Neurol. 41. 432-437 (1997)

[Publications] YX Zhou,: "Machado-Joseph disease in four Chinese pedigrees : Molecular analysis of 15 patients including two juvenile cases and clinical correlations" Neurology. 48. 482-485 (1997)

[Publications] M Oyake,: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA. Strong conservation of a polymorphic CAG repeat in the murine gene" Genomics. 40. 205-207 (1997)

[Publications] K Muraki,: "Severe lactic acidosis and neonatal death Pearson syndrome" J Inher Metab Dis. 20. 43-48 (1997)

[Publications] A Seki,: "Mitochondrial encephalomyopathy with 15915 mutation : case report" Pediatr Neurol. 17. 161-164 (1997)

[Publications] M Ozawa,: "Myoclonus epilepsy associated with ragged-red fibers : A G-TO-A mutation at nucleotide pair 8363 in mitochondrial tRNA^<Lys> in two families" Muscle Nerve. 20. 271-278 (1997)

[Publications] M Okada,: "Effects of carbamazepine on hippocampal serotonergic system." Epilepsy Res. 31・3. 187-198 (1998)

[Publications] M Okada,: "Interaction between Ca^<2+>,K^+ carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode." Brit J Pharmacol. 124. 1277-1285 (1998)

[Publications] S Kaneko: "Pregancy and quality of life in women with epilepsy." Clin Ther. 20 Suppl.A. A30-A47 (1998)

[Publications] M Okada,: "Effects of antiepileptic drugs on K^+-induced glutamate release spreading depression in the hippocampus determined with an in vivo microdyalysis glutamate biosensor(MGB)." Epilepsia. 39 Suppl.5. 56 (1998)

[Publications] K Wada: "Occupational and marital status of patients with epilepsy." Epilepsia. 39 Suppl.5. 66-67 (1998)

[Publications] M Okada,: "Pharmacological interactions between magnesium ion and adenosine on monoaminergic system in the central nervous system." Magnesium Res. 11. 289-305 (1998)

[Publications] 奥村彰久,: "ほぼ同時に発症した「軽症下痢に伴うけいれん」の一卵性双生児例" 脳と発達. 31. 59-62 (1999)

[Publications] 奥村彰久,: "「軽症胃腸炎に伴うけいれん」の臨床像" 小児科臨床. 52. 51-55 (1999)

[Publications] T Sato,: "Transgenic mice harboring a full-length human mutant DRPLA gene exhibit agedependent intergenerational and somatic instabilities of CAG repeats comparable to those in DRPLA patients." Hum Mol Genet. 8・1. 99-106 (1999)

[Publications] 前澤真理子,: "神経性食欲不振症とcontra-coup injury-治療経過と画像診断-" 脳と発達. 31・1. 88-89 (1999)

[Publications] J Ono,: "Ring chromosome 14 complicated with complex partial seizures and hypoplastic corpus callosum." Pediatr Neurol. 20・1. 70-72 (1999)

[Publications] M Okada,: "Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin." Eur J Neurosci. 11. 1-9 (1999)

[Publications] S Kaneko: "Congenital malformations due to antiepileptic drugs." Epilepsy Res. 32. in press (1999)

[Publications] 宮本百合子,: "部分発作とみなされるてんかん発作症状を持つ良性成人型家族性ミオクローヌスてんかん(Benign adult familial myoclonus epilepsy(BAFME)の1家系" てんかん研究. 17・1(印刷中). (1999)

[Publications] S Tobimatsu,: "Chromative sensitive epilepsy-A variant of photosensitive epilepsy." Ann Neurol. (accepted). (1999)

[Publications] H Utsunomiya,: "Development of the temporal lobe in infants and children ; Analysis by MR-based volumetry." Amer J Neuroradiol. (accepted). (1999)

[Publications] 満留昭久,: "テレビアニメ「ポケットモンスター」視聴により誘発された光感受性発作に関する臨床的・脳波学的検討" 厚生科学特別研究「光感受性発作に関する臨床研究」報告書. 71-76 (1998)

[Publications] 飛松省三,: "視覚誘発電位、脳波、脳磁図を用いたポケモン発作の発症機序に関する研究" 厚生科学特別研究「光感受性発作に関する臨床研究」報告書. 113-121 (1998)

[Publications] 大府正治,: "中心・側頭部に棘波を有する良性小児部分てんかん(BECT)における高振幅SEP : 睡眠・覚醒による変化" 脳波と筋電図. 26. 285-291 (1998)

[Publications] 大府正治,: "インフルエンザ脳症後、驚愕てんかんを呈した2例" 臨床脳波. 40. 682-686 (1998)

[Publications] 大府正治,: "乳児重症ミオクロニーてんかん(SMEI)における高振幅体性感覚誘発電位の経時的変化についての研究-周辺群および熱性痙攣との比較-" てんかん治療研究振興財団研究年報. 10. 133-137 (1998)

[Publications] S Igarashi,: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet. 18. 111-117 (1998)

[Publications] M Saito,: "Refinement of the gene locus for autosomal recessive juvenile parkinsonism(AR-JP)on chromosome 6q25.2-27 and identification of markers exhibiting linkage disequilibrium." J Hum Genet. 43. 22-31 (1998)

[Publications] E Sidransky,: "A triplet repeat on 17q accounts for most expansions detected by the repeat expansion detection technique." Amer J Hum Genet. 62・6. 1548-1551 (1998)

[Publications] S Tsuji: "Dentatorubral-pallidoluysian atrophy(DRPLA)." Analysis of Triplet Repeat Disorders,edited by Rubinsztein,D.C.and Hayden,M.R.BIOS Scientific Publishers,Oxford.209-218 (1998)

[Publications] 前澤真理子,: "ローランド棘波とTVモニターにより誘発されたけいれん" 脳波と筋電図. 26・3. 262-263 (1998)

[Publications] 前澤真理子,: "環境ホルモン(外因性内分泌攪乱物質)と小児の診療" 産婦人科の世界. 51・1. 65-69 (1998)

[Publications] A Honda,: "Isolated lissencephaly sequence with balanced chromosome translocation involving 17p13.3." Brain Dev. 20. 190-192 (1998)

[Publications] H Kurahashi,: "Molecular cloning of the chromosomal breakpoint in the LIS1 gene of a patient with isolated lissencephaly and balanced t(8 ; 17)." Hum Genet. 103. 189-192 (1998)

[Publications] M Sakamoto,: "Alteration of the LIS1 gene in Japanese patients with isolated lissencephaly sequence or Miller-Dieker syndrome." Hum Genet. 103. 586-589 (1998)

[Publications] H Takano,: "Close associations between prevalence of dominantly irherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian-populations." Am J Hum Genet. 63・4. 1060-1066 (1998)

[Publications] M Okada,: "Effects of Ca^<2+> channel antagonists on striatal dopamine and DOPA release,studies by in vivo microdialysis." Brit J Pharmacol. 123. 805-814 (1998)

[Publications] CD Ferrie,: "Early onset benign occipital seizure susceptibility syndrome" Epilepsia. 38. 285-293 (1997)

[Publications] K Aso,: "Frontal lobe epilepsy of childhood onset" Epilepsia. 38 Suppl.6. 40-41 (1997)

[Publications] T Ohoki,: "Severe myoclonic epilepsy in infancy evolution of seizures" Seizure. 6. 219-224 (1997)

[Publications] K Wada,: "Prognosis and clinical features of intractable epilepsy : A prospective study" Psychiat Clin Neurosciences. 51. 233-235 (1997)

[Publications] 満留昭久,: "日本人良性新生児けいれん(BFNC)家系でのNicotinic acethylcholine recept or α4 subunit(CHRNA-4)の変異の検索" てんかん治療研究振興財団研究年報. 9. 152-160 (1997)

[Publications] M Ozawa,: "Single muscle fiber analysis in patients with 3243 mutation in mitochondrial DNA : Comparision with the phenotype and the proportion of mutant genome." J Neurol Sci. 159. 170-175 (1998)

[Publications] M Makino,: "Confirmation that a T-to-C mutation at 9176 in mitochondrial DNA is an additional candidate mutation for Leigh's syndrome." Neuromuscul Disord. 8. 149-151 (1998)

[Publications] T Kuroiwa,: "Mitochondrial encephalomyopathy showing prominent microvacuolation and necrosis of intestinal smooth muscle cells : A case diagnosed by rectal biopsy." Acta Neuropathol. 96. 86-90 (1998)

[Publications] S Nishizuka,: "Tissue-specific involvement of multiple mitochondrial DNA deletions in familial mitochondrial myopathy." Biochem Biophys Res Commun. 247. 24-27 (1998)

[Publications] K Watanabe,: "West syndrome : etiological and prognostic aspects." Brain Dev. 20・1. 1-8 (1998)

[Publications] 渡辺一功,: "乳幼児期、児童期のてんかん" 臨床精神医学講座9 てんかん、中山書店、東京. 9. 254-264 (1998)

[Publications] 渡辺一功,: "脳の発達とてんかんの病態" 神経研究の進歩. 42. 954-961 (1998)

[Publications] 奥村彰久,: "早産児に発症したWest症候群-新生児期における脳波所見の経時的変化-" 臨床脳波. 40. 700-704 (1998)

[Publications] A Okumura,: "Evolutional changes and outcome of West syndrome : correlation with magnatic resonance imaging findings." Epilepsia. 39 Suppl.5. 46-49 (1998)

[Publications] Yan Ping Lin,: "Benign myoclonic epilepsy in infants : Video-EEG features and log-term follow-up." Neuropediatr. 29. 268-271 (1998)

[Publications] S Hirose,: "Valproate therapy does not deplete carnitine levels in otherwise healthy children." Pediatrics. 101・5. 1-5 (1998)

兼子直弘前大学, 医学部, 教授 (40106852)