Generalized epilepsy with febrile seizures (febrile seizures With Generalized epilepsy) - Gen GABRG2.
Generalized epilepsy with febrile seizures (FSGS) is a familiar epileptic syndrome characterized by generalized seizure type with a large phenotypic variability, combining febrile seizures, absence seizures, partial seizures, atonic seizures, or myoclonic seizures. This disease can manifest from 3 months of age and persists beyond 6 years. Overall, affected children have febrile seizures later evolve epilepsy with febrile seizures. Sometimes these seizures may occur without fever. The intensity of seizures in this disease is very variable.
This process is due to mutations in the gene GABRG2, located on the long arm of chromosome 5 (5q34). This gene encodes the ?-2 receptor subunit for butyric acid gamma-aminobutyric (GABA).
They have identified at least 3 GABRG2 gene mutations in people with generalized epilepsy with febrile seizures. Mutations in the gene GABRG2 lead to FSGS type III, also known as Dravet syndrome 3, with a more severe phenotype. A heterozygous mutation identified in GABRG2 gene (K289M) affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3, which results in a decrease in the amplitude of the currents chloride channel induced GABA . Another mutation, R43Q, replacing an amino acid residue is highly conserved in the first of two binding domains benzodiazepines. A third mutation identified, Q351, induces a stop codon in the mature protein, with loss of response to GABA, which increases neuronal excitability and seizures.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with epilepsy with febrile seizures generalized by the complete PCR amplification of exons GABRG2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).