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.
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.
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.
Mutations in SCN1A, the gene encoding voltage-gated sodium channel NaV1.1, cause a spectrum of epilepsy disorders that range from genetic epilepsy with febrile seizures plus to catastrophic disorders such as Dravet syndrome.
Phenotypes caused by de novo SCN1A pathogenic variants are very variable, ranging from severely affected patients with Dravet syndrome to much milder genetic epilepsy febrile seizures plus cases.
Genetic alterations in the SCN1A gene coding for the α-subunit of the neuronal voltage-gated sodium ion channel, type 1 (NaV 1.1), is associated with a spectrum of seizure-related disorders in human, ranging from a relatively milder form of febrile seizures to a more severe epileptic condition known as the Dravet syndrome.
Mutations in the GABA-A receptor gamma 2 subunit gene (<i>GABRG2</i>), for example, have been associated with absence epilepsy and febrile seizures in humans.
By performing an association study, we used single-nucleotide polymorphisms to investigate the distribution of genotypes of GABRG2 in patients with FSs.
Using targeted next generation sequencing (NGS), a novel splicing variation (NM_198903.2:c.1249-1G>T) was identified in the γ-aminobutyric acid type A (GABA-A) receptor γ2 subunit (GABRG2) gene of a FS patient.
Mutations in the gamma-aminobutyric acid type A receptor (GABRG2) gene have been associated with generalized epilepsy, childhood absence epilepsy and febrile seizures.
The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea.
TT genotype carriers in SR group were high in FS (with regard to MDR1 gene polymorphism) and GS (with regard to GABRG2 gene polymorphism) compared with a well-controlled seizure group.