| Titre : |
Mutations of Voltage-Gated Sodium Channel Genes SCN1A and SCN2A in Epilepsy, Intellectual Disability, and Autism |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
Kazuhiro YAMAKAWA, Auteur |
| Année de publication : |
2016 |
| Importance : |
p.233-251 |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Autism Dravet syndrome Epilepsy Intellectual disability Nav1.1 Nav1.2 Parvalbumin inhibitory neuron SCN1A SCN2A Sodium channel |
| Index. décimale : |
SCI-D SCI-D - Neurosciences |
| Résumé : |
Mutations of SCN1A and SCN2A were found in a wide spectrum of epilepsies, intellectual disability, and autism. Nav1.1 protein encoded by SCN1A is densely expressed in parvalbumin-positive inhibitory interneurons and moderately in a subpopulation of excitatory neurons. Dravet syndrome model mice (SCN1A+/?) showed epileptic seizure, sudden death, and autistic behavior similar to patients, and conditional knockout mice studies revealed that Nav1.1 haploinsufficiency in inhibitory neurons is the primary cause for those features and that in excitatory neurons it is contrarily ameliorating for seizures and sudden death. Whole-exome sequencing studies on hundreds of autistic patients also showed SCN1A de novo loss of function mutations, but those of SCN2A were far more dominated. SCN2A mutations also appear in patients with epileptic encephalopathies, but those are mostly missense suggesting gain-of-function. Dominant expression of Nav1.2 encoded by SCN2A in excitatory neurons may explain the afebrile nature of the disease and suggest distinct pathological cascades for those with SCN1A mutations. |
| En ligne : |
http://dx.doi.org/10.1016/B978-0-12-800109-7.00015-7 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 |
Mutations of Voltage-Gated Sodium Channel Genes SCN1A and SCN2A in Epilepsy, Intellectual Disability, and Autism [Texte imprimé et/ou numérique] / Kazuhiro YAMAKAWA, Auteur . - 2016 . - p.233-251. Langues : Anglais ( eng)
| Mots-clés : |
Autism Dravet syndrome Epilepsy Intellectual disability Nav1.1 Nav1.2 Parvalbumin inhibitory neuron SCN1A SCN2A Sodium channel |
| Index. décimale : |
SCI-D SCI-D - Neurosciences |
| Résumé : |
Mutations of SCN1A and SCN2A were found in a wide spectrum of epilepsies, intellectual disability, and autism. Nav1.1 protein encoded by SCN1A is densely expressed in parvalbumin-positive inhibitory interneurons and moderately in a subpopulation of excitatory neurons. Dravet syndrome model mice (SCN1A+/?) showed epileptic seizure, sudden death, and autistic behavior similar to patients, and conditional knockout mice studies revealed that Nav1.1 haploinsufficiency in inhibitory neurons is the primary cause for those features and that in excitatory neurons it is contrarily ameliorating for seizures and sudden death. Whole-exome sequencing studies on hundreds of autistic patients also showed SCN1A de novo loss of function mutations, but those of SCN2A were far more dominated. SCN2A mutations also appear in patients with epileptic encephalopathies, but those are mostly missense suggesting gain-of-function. Dominant expression of Nav1.2 encoded by SCN2A in excitatory neurons may explain the afebrile nature of the disease and suggest distinct pathological cascades for those with SCN1A mutations. |
| En ligne : |
http://dx.doi.org/10.1016/B978-0-12-800109-7.00015-7 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 |
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Mutations of Voltage-Gated Sodium Channel Genes SCN1A and SCN2A in Epilepsy, Intellectual Disability, and Autism
