1996 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	07307013
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	大沼悌一国立精神神経センター, 神経研究所第7部, 部長 (30003536) 関亨慶応義塾大学, 医学部, 講師 (70051274) 佐野輝愛媛大学, 医学部附属病院, 助教授 (30178800) 磯村実東京大学, 医科学研究所, 助手 (40272497) 辻省次新潟大学, 脳研究所, 教授 (70150612)
キーワード	てんかん / 熱性けいれん / 遺伝子 / 家系調査 / 連鎖解析
研究概要	てんかんおよび熱性けいれんの原因遺伝子解明を目標に、「てんかん・熱性けいれん(遺伝子)解析に関する共同研究グループ」を設立し、家系収集とサンプリングおよび連鎖解析を進めている。 1996年末の時点で収集できた家系は190家系であり、そのうち40家系でサンプリングが進行中である。家系調査の対象は、特発性てんかん、熱性けいれん、benign infantile familial convulsions、severe myoclonic epilepsy in infancy、benign adult familial myoclonic epilepsyである。特発性てんかんのうち、発端者がchildhood absence epilepsyの家系では、発端者の親子よりも同胞にてんかん罹患者が多く、そのてんかん類型は発端者と同じchildhood absence epilepsyであるものが多かった。同様に、特発性てんかんのうちepilepsy with generalized tonic-clonic seizuresと、benign childhood epilepsy with centrotemporal spikeについても、これらのてんかん類型が発端者にみられる家系では、発端者の親子よりは同胞にてんかん罹患者が多く、同胞のてんかん類型は発端者と同一である傾向が大きいことが示された。熱性けいれんについては23家系が収集されており、現在連鎖解析を開始した。Benign neonatal familial convulsions、juvenile myoclonic epilepsy、benign adult familial myoclonic epilepsy(BAFME)については、連鎖解析を用いての原因遺伝子座位解明のための試みが進行中である。このうち、とくにBAFMEは、遺伝素因の関与の大きいわが国に特有なてんかんの一型であると考えられるが、現在までいくつかの大家系が収集されており、臨床上の特徴を明らかにし近日中に論文を投稿予定である。また、これまでの連鎖解析の結果、BAFMEの原因遺伝子は、6p、8p、12p、21qには存在しないことが明らかになり、その正確な座位が近日中に判明する予定である。

研究成果

(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Sunao Kaneko,et al: "Epilepsy and genetics" Psychiatry and Clinical Neurosciences. 49・3. 199-200 (1995)
[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy (DRPLA) Molecular basis for wide clinical features of DRPLA" Clinical Neuroscience. 3. 23-27 (1995)
[文献書誌] K Sato,et al: "Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?" Neurology. 45・10. 1934-1936 (1995)
[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy (DRPLA) : close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation" Cell Biology. 6. 37-44 (1995)
[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy : Clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat" Annals of Neurology. 37・6. 769-775 (1995)
[文献書誌] Osamu Onodera,et al: "Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS" Am. J. Hum. Genet.57. 1050-1060 (1995)
[文献書誌] Takeshi Ikeuchi,et al: "Non-mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph Disease : The mutant allele is preferentially transmitted in male meiosis" Am. J. Hum. Genet.58. 730-733 (1996)
[文献書誌] Yu-ichi Goto,et al: "Detection of DNA fragments encompassing the deletion junction of mitochondrial genome" Biochemical and Biophysical Research Communications. 222・2. 215-219 (1996)
[文献書誌] Eiji Nakagawa,et al: "Long-term therapy with cytochrome c,flavin mononucleotide and thiamine diphosphate for a patient with kearns-Sayre syndrome" Brain & Development. 18. 68-70 (1996)
[文献書誌] A Kuwano,et al: "Benign adult familial myoclonus epilepsy (BAFME) : an autosomal dominant form not linked to dentatorubral pallidoluysian atrophy (DRPLA) gene" J Med Genet. 33. 80-81 (1996)
[文献書誌] Kazuyoshi Watanabe: "Medical treatment of West syndrome in Japan" Journal of Child Neurology. 10・2. 143-147 (1995)
[文献書誌] Yoshiko Haga,et al: "Asymmetric spasms in West syndrome" J. Epilepsy. 8・1. 61-67 (1995)
[文献書誌] Yoshiko Haga,et al: "Do ictal,clinical,and electroencephalograrhic features predict outcome in West syndrome?" Pediatric Neurology. 13・3. 226-229 (1995)
[文献書誌] Akihisa Okumura,et al: "Periventricular leukomalacia and West syndrome" Development and Medicne and Child Neurology. 38. 13-18 (1996)
[文献書誌] Akihisa Okumura,et al: "Benign partial epilepsy in infancy" Archives of Disease in Childhood. 74. 19-21 (1996)
[文献書誌] Hiroki Takano,et al: "Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy : Cellular population-dependent dynamics of mitotic instability" The American Journal of Human Genetics. 58・6. 1212-1222 (1996)
[文献書誌] Osamu Komure,et al: "DNA analysis in hereditary dentatorubral-pallidoluysian atrophy : Correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation" Neurology. 45・1. 143-149 (1995)
[文献書誌] Shuichi Ueno,et al: "Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA)" Human Molecular Genetics. 4・4. 663-666 (1995)
[文献書誌] Hiroko Yanagisawa,et al: "A unique origin and multistep process for the generation of expanded DRPLA triplet repeats" Human Molecular Genetics. 5・3. 373-379 (1996)
[文献書誌] Teiichi Onuma: "Historical perspectives in epileptic psychosis in Japan" Psychiatry and Clinical Neurosciences. 49. 179-183 (1995)
[文献書誌] Michikazu Nakamura,et al: "A novel point mutation in the mitochondrial tRNA_<ser(UCN)> gene detected in a family with MERRF/MELAS overlap syndrome" Biochemical and Biophysical Research Communications. 214・1. 86-93 (1995)
[文献書誌] Matsuko Ozawa,et al: "The 8,344 mutation in mitochondrial DNA : A comparison between the proportion of mutant DNA and clinicopathologic findings" Neuromusc. Disord.5・6. 483-488 (1995)
[文献書誌] Yu-ichi Goto: "Clinical features of melas and mitochondrial DNA mutations" Muscle & Nerve. Suppl 3. 107-112 (1995)
[文献書誌] Kazuyoshi Watanabe: "Recent advances and some problems in the delineation of epileptic syndromes in children" Brain & Development. 18. 423-437 (1996)
[文献書誌] 千葉丈司,他: "てんかんと遺伝子異常" 小児内科. 27・8. 1197-1201 (1995)
[文献書誌] 兼子直,他: "てんかん・熱性けいれん遺伝(子)解析に関する多施設共同研究-家系調査報告:予報-" てんかん治療研究振興財団研究年報. 8. 80-90 (1996)
[文献書誌] 兼子直,他: "てんかんの分子生物学的研究" 精神医学. 38・11. 1155-1161 (1996)
[文献書誌] 前澤真理子,他: "小児欠神てんかん" 小児内科. 27・9. 55-59 (1995)
[文献書誌] 寺田倫,他: "精神分裂病の遺伝負因が濃厚なてんかん患者にみられた幻覚妄想状態" 臨床精神医学. 24・9. 1223-1228 (1995)
[文献書誌] 西脇俊二,他: "幻覚妄想状態を呈したてんかん患者におけるSchneiderの一級症状前頭葉てんかんと側頭葉てんかんの比較" 精神医学. 38・4. 393-398 (1996)
[文献書誌] 廣瀬伸一,他: "良性家族性新生児けいれん" 小児科の進歩. 16. 104-108 (1996)
[文献書誌] 小国美也子,他: "若年性ミオクロニ-てんかん(Janz症候群)における臨床遺伝学的,遺伝子工学的基礎研究" てんかん治療研究振興財団研究年報. 8. 73-79 (1996)
[文献書誌] Kazuyoshi Watanabe: "Epilepsy in children Benign partial epilepsies" Chapman & Hall,London, 21 (1996)

1996 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] Sunao Kaneko,et al: "Epilepsy and genetics" Psychiatry and Clinical Neurosciences. 49・3. 199-200 (1995)

[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy (DRPLA) Molecular basis for wide clinical features of DRPLA" Clinical Neuroscience. 3. 23-27 (1995)

[文献書誌] K Sato,et al: "Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?" Neurology. 45・10. 1934-1936 (1995)

[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy (DRPLA) : close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation" Cell Biology. 6. 37-44 (1995)

[文献書誌] Takeshi Ikeuchi,et al: "Dentatorubral-pallidoluysian atrophy : Clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat" Annals of Neurology. 37・6. 769-775 (1995)

[文献書誌] Osamu Onodera,et al: "Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS" Am. J. Hum. Genet.57. 1050-1060 (1995)

[文献書誌] Takeshi Ikeuchi,et al: "Non-mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph Disease : The mutant allele is preferentially transmitted in male meiosis" Am. J. Hum. Genet.58. 730-733 (1996)

[文献書誌] Yu-ichi Goto,et al: "Detection of DNA fragments encompassing the deletion junction of mitochondrial genome" Biochemical and Biophysical Research Communications. 222・2. 215-219 (1996)

[文献書誌] Eiji Nakagawa,et al: "Long-term therapy with cytochrome c,flavin mononucleotide and thiamine diphosphate for a patient with kearns-Sayre syndrome" Brain & Development. 18. 68-70 (1996)

[文献書誌] A Kuwano,et al: "Benign adult familial myoclonus epilepsy (BAFME) : an autosomal dominant form not linked to dentatorubral pallidoluysian atrophy (DRPLA) gene" J Med Genet. 33. 80-81 (1996)

[文献書誌] Kazuyoshi Watanabe: "Medical treatment of West syndrome in Japan" Journal of Child Neurology. 10・2. 143-147 (1995)

[文献書誌] Yoshiko Haga,et al: "Asymmetric spasms in West syndrome" J. Epilepsy. 8・1. 61-67 (1995)

[文献書誌] Yoshiko Haga,et al: "Do ictal,clinical,and electroencephalograrhic features predict outcome in West syndrome?" Pediatric Neurology. 13・3. 226-229 (1995)

[文献書誌] Akihisa Okumura,et al: "Periventricular leukomalacia and West syndrome" Development and Medicne and Child Neurology. 38. 13-18 (1996)

[文献書誌] Akihisa Okumura,et al: "Benign partial epilepsy in infancy" Archives of Disease in Childhood. 74. 19-21 (1996)

[文献書誌] Hiroki Takano,et al: "Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy : Cellular population-dependent dynamics of mitotic instability" The American Journal of Human Genetics. 58・6. 1212-1222 (1996)

[文献書誌] Osamu Komure,et al: "DNA analysis in hereditary dentatorubral-pallidoluysian atrophy : Correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation" Neurology. 45・1. 143-149 (1995)

[文献書誌] Shuichi Ueno,et al: "Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA)" Human Molecular Genetics. 4・4. 663-666 (1995)

[文献書誌] Hiroko Yanagisawa,et al: "A unique origin and multistep process for the generation of expanded DRPLA triplet repeats" Human Molecular Genetics. 5・3. 373-379 (1996)

[文献書誌] Teiichi Onuma: "Historical perspectives in epileptic psychosis in Japan" Psychiatry and Clinical Neurosciences. 49. 179-183 (1995)

[文献書誌] Michikazu Nakamura,et al: "A novel point mutation in the mitochondrial tRNA_<ser(UCN)> gene detected in a family with MERRF/MELAS overlap syndrome" Biochemical and Biophysical Research Communications. 214・1. 86-93 (1995)

[文献書誌] Matsuko Ozawa,et al: "The 8,344 mutation in mitochondrial DNA : A comparison between the proportion of mutant DNA and clinicopathologic findings" Neuromusc. Disord.5・6. 483-488 (1995)

[文献書誌] Yu-ichi Goto: "Clinical features of melas and mitochondrial DNA mutations" Muscle & Nerve. Suppl 3. 107-112 (1995)

[文献書誌] Kazuyoshi Watanabe: "Recent advances and some problems in the delineation of epileptic syndromes in children" Brain & Development. 18. 423-437 (1996)

[文献書誌] 千葉丈司,他: "てんかんと遺伝子異常" 小児内科. 27・8. 1197-1201 (1995)

[文献書誌] 兼子直,他: "てんかん・熱性けいれん遺伝(子)解析に関する多施設共同研究-家系調査報告:予報-" てんかん治療研究振興財団研究年報. 8. 80-90 (1996)

[文献書誌] 兼子直,他: "てんかんの分子生物学的研究" 精神医学. 38・11. 1155-1161 (1996)

[文献書誌] 前澤真理子,他: "小児欠神てんかん" 小児内科. 27・9. 55-59 (1995)

[文献書誌] 寺田倫,他: "精神分裂病の遺伝負因が濃厚なてんかん患者にみられた幻覚妄想状態" 臨床精神医学. 24・9. 1223-1228 (1995)

[文献書誌] 西脇俊二,他: "幻覚妄想状態を呈したてんかん患者におけるSchneiderの一級症状 前頭葉てんかんと側頭葉てんかんの比較" 精神医学. 38・4. 393-398 (1996)

[文献書誌] 廣瀬伸一,他: "良性家族性新生児けいれん" 小児科の進歩. 16. 104-108 (1996)

[文献書誌] 小国美也子,他: "若年性ミオクロニ-てんかん(Janz症候群)における臨床遺伝学的,遺伝子工学的基礎研究" てんかん治療研究振興財団研究年報. 8. 73-79 (1996)

[文献書誌] Kazuyoshi Watanabe: "Epilepsy in children Benign partial epilepsies" Chapman & Hall,London, 21 (1996)

1996 年度実績報告書

兼子直弘前大学, 医学部, 教授 (40106852)

[文献書誌] 西脇俊二,他: "幻覚妄想状態を呈したてんかん患者におけるSchneiderの一級症状前頭葉てんかんと側頭葉てんかんの比較" 精神医学. 38・4. 393-398 (1996)