Furthermore, four loci were associated with febrile seizures in general, implicating the sodium channel genes SCN1A (rs6432860: P = 2.2 × 10(-16)) and SCN2A (rs3769955: P = 3.1 × 10(-10)), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)).
Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation.
We sequenced the 5' upstream region of SCN1A in 166 patients with epilepsy and febrile seizures who were negative for point mutations in the coding regions or genomic rearrangements.
Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure.
It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes.
SCN1A mutations are associated with a spectrum of seizure-related disorders, ranging from a relatively mild form of febrile seizures to a more severe epileptic encephalopathy known as Dravet syndrome.
We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation.
The fact that we identify mouse FS-QTL2a with high FEB3 homology is strong support for the validity of the eFS mouse model to study genetics of human FS.
SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context).
One patient has a family history consistent with the family epilepsy syndrome diagnosis of GEFS+, whilst the second has a de novo SCN1A mutation in the setting of "severe" Febrile Seizures.
We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families.
Severe myoclonic epilepsy of infancy (SMEI, also known as Dravet syndrome) and genetic epilepsy with febrile seizures plus (mild febrile seizures) can both arise due to mutations of SCN1A, the gene encoding alpha 1 pore-forming subunit of the Nav1.1 voltage-gated sodium channel.