| Project/Area Number |
16591068
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | RIKEN |
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Principal Investigator |
YAMAKAWA Kazuhiro RIKEN, Lab.For Neurogenetics, Laboratory Head, 神経遺伝研究チーム, チームリーダー (30241235)
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| Co-Investigator(Kenkyū-buntansha) |
OGIWARA Ikuo RIKEN, Lab.For Neurogenetics, 神経遺伝研究チーム, 研究員 (30373286)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Epilepsy / Sodium channel / Genes / SCN2A / SMEI / GEFS+ / Nonsense mutation / Patch-clamp analysis / GEFS_+ |
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| Research Abstract |
Recently, multiple mutations of voltage-gated sodium channel genes have been reported in patients with epilepsies including generalized epilepsy with febrile siezures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI). Many of the mutations were reported in the SCN1A gene, but previously we reported a missense mutation of SCN2A gene in a patient with GEFS+.
In this research project, we found a truncation mutation of SCN2A gene in a patient with intractable epilepsy with severe mental decline and reported in a internationally reputed journal (Kamiya et al., 2004). We also found that the truncated protein has a dominant-negative effect that possibly elucidate the disease mechanism. In order to further investigate the mechanism, we are trying to make a knock-in mouse with the SCN2A truncation mutation. The construction of the targeting vector was completed and the generation of the mice are now in trial. For the SCN1A studies, we reported a functional analysis of a mutation found in an atypical SMEI, ICEGTC (Rhodes et al., 2005). We also reported a familial case of SMEI (Kimura et al., 2005) and a new case of GEFS+ (Nagao et al., 2005).
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