Dravet syndrome (WP5200)
Homo sapiens
Dravet syndrome is a rare form of epilepsy. Between 70% and 80% of patients carry sodium channel α1 subunit gene (SCN1A) loss of function mutations. Truncating mutations (early stop codon) account for about 40% and have a significant correlation with an earlier age of seizures onset. The mutations lead to haploinsufficiency of the voltage-gated sodium channel α subunit NaV1.1 in the of GABAergic inhibitory interneurons in the brain. Mutations in other genes like KCNA1, CHD2, PCDH19 and STXBP1 can also lead to Dravet syndrome.
Authors
Miriam Babukhian , Lea Doerner , Egon Willighagen , Friederike Ehrhart , and Pepin MarshallActivity
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Organisms
Homo sapiensCommunities
Rare DiseasesAnnotations
Cell Type Ontology
neuron GABAergic interneuronDisease Ontology
Dravet syndromePathway Ontology
disease pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| K+ | Metabolite | chebi:29103 | |
| Ca2+ | Metabolite | chebi:29108 | |
| GABA | Metabolite | chebi:16865 | |
| Syntaxin | Metabolite | wikidata:Q390407 | |
| Na+ | Metabolite | chebi:29101 | |
| Na+ | Metabolite | chebi:29101 | |
| K+ | Metabolite | chebi:29103 | |
| GABA | Metabolite | chebi:16865 | |
| Na+ | Metabolite | chebi:29101 | |
| K+ | Metabolite | chebi:29103 | |
| SCN1A | GeneProduct | ensembl:ENSG00000144285 | |
| PRR5L | Protein | uniprot:Q6MZQ0 | |
| PRKCA | Protein | uniprot:P17252 | |
| MLST8 | Protein | uniprot:Q9BVC4 | |
| Nav1.6 | Protein | uniprot:Q9UQD0 | |
| Nav1.2 | Protein | uniprot:Q99250 | |
| PRR5 | Protein | uniprot:P85299 | |
| Kv1.2 | Protein | uniprot:P16389 | |
| FGF13 | Protein | uniprot:Q92913 | |
| MAPKAP1 | Protein | uniprot:Q9BPZ7 | |
| STXBP1 | Protein | uniprot:P61764 | |
| SCN3B | Protein | uniprot:Q9NY72 | |
| NFKB1 | Protein | uniprot:P19838 | |
| HCN1 | Protein | uniprot:O60741 | |
| Nav1.1 | Protein | uniprot:P35498 | |
| CHD2 | Protein | uniprot:O14647 | |
| CAMK2A | Protein | uniprot:Q9UQM7 | |
| PCDH19 | Protein | uniprot:Q8TAB3 | |
| RICTOR | Protein | uniprot:Q6R327 | |
| Nav1.3 | Protein | uniprot:Q9NY46 | |
| PIK3CA | Protein | uniprot:P42336 | |
| SCN2B | Protein | uniprot:O60939 | |
| MTOR | Protein | uniprot:P42345 | |
| TNF | Protein | uniprot:P01375 | |
| AKT1 | Protein | uniprot:P31749 | |
| CALM1 | Protein | uniprot:P0DP23 | |
| MAPK11 | Protein | uniprot:Q15759 | |
| SCN1B | Protein | uniprot:Q07699 | |
| SCN4B | Protein | uniprot:Q8IWT1 | |
| Nav1.1 | Protein | uniprot:P35498 | |
| STXBP1 | Protein | uniprot:P61764 | |
| Nav1.3 | Protein | uniprot:Q9NY46 |
References
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- Mice lacking sodium channel beta1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture. Chen C, Westenbroek RE, Xu X, Edwards CA, Sorenson DR, Chen Y, et al. J Neurosci. 2004 Apr 21;24(16):4030–42. PubMed Europe PMC Scholia
- Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Wierda KDB, Toonen RFG, de Wit H, Brussaard AB, Verhage M. Neuron. 2007 Apr 19;54(2):275–90. PubMed Europe PMC Scholia
- Identification of novel interaction sites that determine specificity between fibroblast growth factor homologous factors and voltage-gated sodium channels. Wang C, Wang C, Hoch EG, Pitt GS. J Biol Chem. 2011 Jul 8;286(27):24253–63. PubMed Europe PMC Scholia
- Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel. Gaudioso C, Carlier E, Youssouf F, Clare JJ, Debanne D, Alcaraz G. Biochem Biophys Res Commun. 2011 Jul 29;411(2):329–34. PubMed Europe PMC Scholia
- Tumor necrosis factor-α enhances voltage-gated Na⁺ currents in primary culture of mouse cortical neurons. Chen W, Sheng J, Guo J, Gao F, Zhao X, Dai J, et al. J Neuroinflammation. 2015 Jun 26;12:126. PubMed Europe PMC Scholia
- Voltage-Gated Sodium Channel β Subunits and Their Related Diseases. Bouza AA, Isom LL. Handb Exp Pharmacol. 2018;246:423–50. PubMed Europe PMC Scholia
- mTOR signalling and cellular metabolism are mutual determinants in cancer. Mossmann D, Park S, Hall MN. Nat Rev Cancer. 2018 Dec;18(12):744–57. PubMed Europe PMC Scholia
- Dravet syndrome as part of the clinical and genetic spectrum of sodium channel epilepsies and encephalopathies. Mei D, Cetica V, Marini C, Guerrini R. Epilepsia. 2019 Dec;60 Suppl 3:S2–7. PubMed Europe PMC Scholia