This mutation alters a cysteine involved in a disulfide bond in the extracellular N-terminus of the protein. This extracellular region is similar to the cell adhesion molecule contactin and other cell adhesion molecules. It is believed that the disulfide bond disrupted by the C121W mutation is required for the proper folding of this N-terminus motif. Coexpression of SCN1B with sodium channel α subunits in oocytes and other cells results in channels that inactivate more slowly. Expression of C121W mutant along with wild-type α subunits produces current indistinguishable from that through α subunits alone. Further investigation of this mutation has indicated that it results in decreased frequency dependent rundown and, thus, likely hyperexcitability when compared to cells expressing the wild-type subunit. This mutation also disrupts the subunits ability to induce cellular aggregation. The importance of this last fact is unclear, though it is presumed that proper channel aggregation within cells and cell-cell contact are required for normal neuronal function.A second mutation has been found in one kindred with GEFS+ type 1. This mutation is in a splice acceptor site of exon 3. The loss of this acceptor site reveals a downstream cryptic acceptor site and a protein missing 5 amino acids in the N-terminus (I70_E74del). This mutation has not been further characterized. Type 2
A second subtype of GEFS+, type 2, is the result of mutations in SCN1A, a gene encoding a sodium channel α subunit. There are currently almost 90 known mutations in the SCN1A gene throughout the entirety of the channel (see table 1).
The result of this mutation is completely non-functional channels and membrane hypoexcitability. The truncated mutant protein also seems to cause wild-type channels to inactivate at more hyperpolarized potentials, indicating that it also acts in a dominant negative manner. Management
Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam. Ketogenic diet has also been found useful in certain cases Management of breakthrough seizures is by benzodiazepine such as midazolam. See also
Febrile seizures
Idiopathic generalized epilepsy
Dravet Syndrome Foundation
International Dravet Epilepsy Action League

References


== External links ==