| Project/Area Number |
12307019
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Hirosaki University |
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Principal Investigator |
KANEKO Sunao Hirosaki University, School of Medicine, Neuropsychiatry, Professor, 医学部, 教授 (40106852)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUDOME Akihisa Fukuoka University, School of Medicine, Pediatrics, Professor, 医学部, 教授 (30038749)
SANO Akira Kagoshima University, School of Medicine, Neuropsychiatry, Professor, 医学部, 教授 (30178800)
TSUJI Shoji The University of Tokyo, Graduate School of Medicine, Neuroscience Division, Neurology, Professor, 医学系研究科, 教授 (70150612)
ITO Masatoshi Shiga Medical Center for Children, Pediatrics, Health dircti manager, 部長 (90135567)
YAMAKAWA Kazuhiro RIKEN, Brain Science Institute, Neurogenetics, Team-leader, 脳科学総合センター, チームリーダー (30241235)
中村 祐輔 東京大学, 医科学研究所・ヒトゲノム解析センター, 教授 (70217909)
大沼 悌一 国立療養所, 犀潟病院, 院長 (30003536)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥41,390,000 (Direct Cost: ¥36,200,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2001: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2000: ¥18,900,000 (Direct Cost: ¥18,900,000)
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| Keywords | Severe myoclonic epilepsy in infancy / Chorea-acanthocytosis / Autosomal dominant nocturnal frontal lobe epilepsy / Benign familial neonatal convulsions / Benign adult familial myoclonic epilepsy / Febrile seizure plus / Channelopathy / Functions of mutated epilepsy genes / 熱性けいれん / 遺伝子 / 家系調査 / 連鎖解析 |
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| Research Abstract |
This report summarizes our own discoveries of novel mutations in the genes of various epilepsy phenotypes, and of the main results of functional analyses of the mutated genes.
As a cause of benign familial neonatal convulsions (BFNC), we identified mutations of KCNQ2 and KCNQ3. The pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC are associated with the interaction between age-dependent reduction of inhibitory KCNQ-channel activity and age-dependent functional switching of GABAergic-system from excitatory to inhibitory action in neonatal CNS. A mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α4 subunit associated with autosomal dominant nocturnal frontal lobe epilepsy caused faster desensitization of rat receptor expressed in oocytes.
We identified a novel gene in the EJM1 region on chromosome 6p12-p11 in families with JME (in contribution), and also identified a previously unknown, full-length of cDNA encoding a presumably structural protein, which we named chorein, in patients with chorea-acanthocytosis.
We reported that autosomal dominant epilepsy with febrile seizure plus and severe myoclonic epilepsy of infancy were associated with various mutations of genes encoding both Na^+ channel subunit (SCN1A, SCN2A) and γ2-subunit of the GABA-A receptor (GABRG2).
Laforin (a cytoplasmic protein associated primarily with polyribosome) is a dual-specificity phosphatase coded by the EPM2A gene defective in Lafora's disease. Exon 1 mutations of EPM2A was associated with an early-onset cognitive deficit subphenotype.
Genes responsible for common phenotypes of epilepsy have been uncovered yet, however, these will undoubtedly be discovered soon.
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