2006 Fiscal Year Final Research Report Summary
Early diagnosis and genetic analysis of severe myoclonic epilepsy in infancy
| Project/Area Number |
16591030
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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 | Okayama University |
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Principal Investigator |
OHTSUKA Yoko Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (10213779)
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| Co-Investigator(Kenkyū-buntansha) |
OHMORI Iori Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (20403488)
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| Project Period (FY) |
2004 – 2006
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| Keywords | severe myoclonic epilepsy in infancy / SCN1A mutations / febrile seizure / functional analysis / SMEI / fever / gene / hot water-induced seizure |
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| Research Abstract |
RESEARCH RESULTS
In order to clarify basic mechanisms of severe myoclonic epilepsy in infancy (SMEI) and promote the early diagnosis of SMEI, we performed the following two studies.
(1) Mutation screen and functional analysis for sodium channel alpha 1 subunit in SMEI Mutations were detected in 33 cases (80.5%) of 41 patients with SMEI. The detection rate of SCN1A mutation was 75% in typical SMEI (TSMEI) patients who had myoclonic seizures and/or atypical absences, and 84% in borderline SMEI (BSMEI) who have only segmental myoclonus. As regards functional analysis, R931C mutation exhibited a significant reduction of current density by whole-cell patch clamp. Green-fluorescence-protein fused R931C showed dominant intensity at the cell surface. These findings suggest the R931C mutation disables the ability to conduction.
(2) Clinical and genetic study of children with a history of febrile seizures and/or hot water-induced seizures before one year of age
Among 96 patients who experienced febr
… More
ile seizures and/or hot water-induced seizures before one year of age, 46 patients were diagnosed as having SMEI and 50 patients were not. Twenty-two of the 50 patients with non-SMEI had only febrile seizures and/or hot water-induced seizures, and remaining 28 had also experienced afebrile seizures. The epileptic syndromes of 25 of these 28 patients were unable to be classified into a specific epileptic syndrome. These patients had similar clinical features to generalized epilepsy accompanied by febrile seizure (GEFS+) except for autosomal dominant inheritance. The other three patients consisted of two with benign childhood epilepsy with centrotemporal spike and one with GEFS+. SCN1A mutations were detected in six of the 50 patients (12%) with non-SMEI. All of these were misssense mutations. All patients with SCN1A mutations had afebrile seizures as well. The detection rate of mutation in these patients was 21.4% (6/28 patients). Detailed analyses of clinical features of the six patients with SCN1A mutations revealed that they had some common characteristics with SMEI: (1) seizures easily induced by fever and/or hot water, (2) history of status epilepticus, (3) association of complex partial seizures, (4) family history of seizures. All except one had hemiconvulsions. None of the six patients had mental retardation. These results indicate that patients with SCN1A mutations display wider variety of clinical features than previously thought. Less
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