1997 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)	大沼悌一国立精神神経センター, 神経研究所第7部, 部長 (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) 磯村実東京大学, がん化学療法センター・ゲノム解析研究部, 助手 (40272497) 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	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。 1997年末の時点で収集できた家系は210家系であり、そのうち50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 familial infantile convulsions、severe myoclonic epilepsy in infancy、benign adult familial myoclonic epilepsyである。特発性てんかんのうち、childhood absence epilepsy、epilepsy with grand mal seizures on awakening、benign childhood epilepsy with centrotemporal spikeについては、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。これらのてんかん類型については、現在連鎖解析を開始したが、epilepsy with grand mal seizures on awakeningの原因遺伝子座位は第6、8、10染色体には存在しないことが判明した。Benign familial neonatal convulsionsについては、罹患家系でのNicotinic acetyicoline receptor α4 subunit(CHRNA-4)の変異の有無について解析中である。Juvenile myoclonic epilepsyについては、罹患家系における連鎖解析の結果、染色体6p21.2-p11領域に関してpositiveな1od scoreを得たが、現在症例数を増して更なる検索を進めている。熱性けいれんについては28家系が収集されており、現在連鎖解析が進行中である。Benign adult familial myoclonic epilepsy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が、これまでの大家系における連鎖解析の結果、その原因遺伝子座位が特定され、近日中に報告される。

Research Products

(44 results)

All Other

All Publications (44 results)

[Publications] Sunao Kaneko, et al: "Epilepsy and genetics" Psychiatry and Clinical Neurosciences. 49・3. 199-200 (1995)
[Publications] Takeshi Ikeuchi, et al.: "Dentatorubral-pallidoluysian atrophy (DRPLA) Molecular basis for wide clinical features of DRPLA" Clinical Neuroscience. 3. 23-27 (1995)
[Publications] K Sato, et al: "Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?" Neurology. 45・10. 1934-1936 (1995)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Shuichi Ueno, et al: "Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA)" Human Molecular Genetics. 4・4. 663-666 (1995)
[Publications] Teiichi Onuma: "Historical perspectives in epileptic psychosis in Japan" Psychiatry and Clinical Neurosciences. 49. 179-183 (1995)
[Publications] 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)
[Publications] 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)
[Publications] Yu-ichi Goto: "Clinical features of melas and mitochondrial DNA mutations" Muscle & Nerve. Suppl 3. 107-112 (1995)
[Publications] Kazuyoshi Watanabe: "Medical treatment of West syndrome in Japan" Journal of Child Neurology. 10・2. 143-147 (1995)
[Publications] Yoshiko Haga, et al: "Asymmetric spasms in West syndrome" J.Epilepsy. 8・1. 61-67 (1995)
[Publications] Yoshiko Haga, et al: "Do ictal,clinical,and electroencephalograrhic features predict outcome in West syndrome?" Pediatric Neurology. 13・3. 226-229 (1995)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] A Kuwano, et al: "Binign adult familial myoclonus epilepsy (BAFME): an autosomal dominant form not linked to dentatorubral pallidoluysian atrophy (DRPLA) gene" J Med Genet. 33. 80-81 (1996)
[Publications] Akihisa Okumura, et al: "Periventricular leukomalacia and West syndrome" Development and Medicne and Child Neurology. 38. 13-18 (1996)
[Publications] Akihisa Okumura, et al: "Benign partial epilepsy in infancy" Archives of Disease in Childhood. 74. 19-21 (1996)
[Publications] Kazuyoshi Watanabe: "Recent advances and some problems in the delineation of epileptic syndromes in children" Brain & Development. 18. 423-437 (1996)
[Publications] S Igarashi, et al: "Intergeneration instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome : implications for the molecular mechanisms of the CAG repeat" Human Molecular Genetics. 5・7. 923-932 (1996)
[Publications] M Isomura, et al: "Cloning and mapping of a novel human cDNA homologous to DROER,the enhancer of the Drosophila melanogaster rudimentary gene" Genomics. 32. 125-127 (1996)
[Publications] M Inoue, et al: "Isolation and characterization of human cDNA clone (GCN5L1) homologous to GCN5,a yeast transcription activator" Cytogenet and Cell Genet. 73. 134-136 (1996)
[Publications] S Ninomiya, et al: "Isolation of a testis-specific cDNA chromosome 17q from a region adjacent to the breakpoint of t(12;17) observed in a patient with acampomelic campomelic dysplasia and sex reversal" Human Molecular Genetics. 5. 69-72 (1996)
[Publications] A Mitsudome, et al: "Rhythmic slow activity in benign childhood epilepsy with centro-temporal spikes" Clinical Electroencephalogr. 28. 44-48 (1996)
[Publications] T Miyajima, et al: "Characteristics of a detected measles gene in cerebrospinal fluid and the adverse effect of high-dose immunoglobulin : Therapy in a case of intractable epilepsy with mental deterioration (second report)" Epilepsia. 37(Suppl.3). 94-95 (1996)
[Publications] H Yamadera, et al: "Epilepsia and ring 20 syndrome" Epilepsia. 37(Suppl.3). 70 (1996)
[Publications] T Takenaka, et al: "Coxistance of gene nutation causing Fabry disease and Duchenne muscular dystrophy in a Japanese boy" Clin Genet. 49. 255-260 (1996)
[Publications] S Tsuji, et al: "Unstable expansion of triplet repeats as a new mechanism for neurodegenerative diseases" Internal Medicine. 36. 3-8 (1997)
[Publications] S Igarashi, et al: "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, et al: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9" Ann Neurol. 41. 432-437 (1997)
[Publications] YX Zhou, et al: "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, et al: "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, et al: "Severe lactic acidosis and neonatal death in Pearson syndrome" J Inher Metab Dis. 20. 43-48 (1997)
[Publications] A Seki, et al: "Mitochondrial encephalomyopathy with 15915 mutation : case report" Pediatr Neurol. 17. 161-164 (1997)
[Publications] M Ozawa, et al: "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] CD Ferrie, et al: "Early onset benign occipital seizure susceptibility syndrome" Epilepsia. 38. 285-293 (1997)
[Publications] K Aso, et al: "Frontal lobe epilepsy of childhood onset" Epilepsia. 38(Suppl.6). 40-41 (1997)
[Publications] T Ohoki, et al: "Severe myoclonic epilepsy in infancy evolution of seizures" Seizure. 6. 219-224 (1997)
[Publications] K Wada, et al: "Prognosis and clinical features of intractable epilepsy : A prospective study" Psychiat Clin Neurosciences. 51. 233-235 (1997)

1997 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] Sunao Kaneko, et al: "Epilepsy and genetics" Psychiatry and Clinical Neurosciences. 49・3. 199-200 (1995)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

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

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

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

[Publications] S Igarashi, et al: "Intergeneration instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome : implications for the molecular mechanisms of the CAG repeat" Human Molecular Genetics. 5・7. 923-932 (1996)

[Publications] M Isomura, et al: "Cloning and mapping of a novel human cDNA homologous to DROER,the enhancer of the Drosophila melanogaster rudimentary gene" Genomics. 32. 125-127 (1996)

[Publications] M Inoue, et al: "Isolation and characterization of human cDNA clone (GCN5L1) homologous to GCN5,a yeast transcription activator" Cytogenet and Cell Genet. 73. 134-136 (1996)

[Publications] S Ninomiya, et al: "Isolation of a testis-specific cDNA chromosome 17q from a region adjacent to the breakpoint of t(12;17) observed in a patient with acampomelic campomelic dysplasia and sex reversal" Human Molecular Genetics. 5. 69-72 (1996)

[Publications] A Mitsudome, et al: "Rhythmic slow activity in benign childhood epilepsy with centro-temporal spikes" Clinical Electroencephalogr. 28. 44-48 (1996)

[Publications] T Miyajima, et al: "Characteristics of a detected measles gene in cerebrospinal fluid and the adverse effect of high-dose immunoglobulin : Therapy in a case of intractable epilepsy with mental deterioration (second report)" Epilepsia. 37(Suppl.3). 94-95 (1996)

[Publications] H Yamadera, et al: "Epilepsia and ring 20 syndrome" Epilepsia. 37(Suppl.3). 70 (1996)

[Publications] T Takenaka, et al: "Coxistance of gene nutation causing Fabry disease and Duchenne muscular dystrophy in a Japanese boy" Clin Genet. 49. 255-260 (1996)

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

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

[Publications] YX Zhou, et al: "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, et al: "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, et al: "Severe lactic acidosis and neonatal death in Pearson syndrome" J Inher Metab Dis. 20. 43-48 (1997)

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

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

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

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

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

兼子直弘前大学, 医学部, 教授 (40106852)