Mutations in the voltage-gated sodium channel subunit gene SCN1A have been associated with febrile seizures (FSs) in autosomal dominant generalized epilepsy with febrile seizures plus (GEFS+) families and severe myoclonic epilepsy of infancy.
As we could not find SCN1A mutations in their parents, one of critical causes of SME may be de novo mutation of the SCN1A gene occurred in the course of meiosis in the parents.
To investigate the possible correlation between genotype and phenotype of epilepsy, we analyzed the voltage-gated sodium channel alpha1-subunit (SCN1A) gene, beta1-subunit (SCN1B) gene, and gamma-aminobutyric acid(A) receptor gamma2-subunit (GABRG2) gene in DNAs from peripheral blood cells of 29 patients with severe myoclonic epilepsy in infancy (SME) and 11 patients with other types of epilepsy.
To investigate the possible correlation between genotype and phenotype of epilepsy, we analyzed the voltage-gated sodium channel alpha1-subunit (SCN1A) gene, beta1-subunit (SCN1B) gene, and gamma-aminobutyric acid(A) receptor gamma2-subunit (GABRG2) gene in DNAs from peripheral blood cells of 29 patients with severe myoclonic epilepsy in infancy (SME) and 11 patients with other types of epilepsy.
To clarify the genotypic differences in this group of epilepsies, we searched for SCN1A abnormalities in 25 patients with SMEI and 10 with ICEGTC, together with the family members of 15 patients.
Our study demonstrates that GABRG2 is not a commonly involved in the etiology of SMEI and suggests that other and yet unidentified genes are involved in the syndrome
In order to further investigate the role of SCN1A and GABRG2 in the pathogenesis of SMEI we have screened for mutations three families with at least two members affected by Dravet syndrome.
In order to further investigate the role of SCN1A and GABRG2 in the pathogenesis of SMEI we have screened for mutations three families with at least two members affected by Dravet syndrome.
The authors analyzed SCN1A mutations in 93 patients with SMEI and made genotype-phenotype correlation to clarify the role of this gene in the etiology of SMEI.
Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na(+) channel alpha-subunit type I (Na(v)1.1) have been identified in patients with SMEI.
In conclusion, our data provide evidence for a wide spectrum of sodium channel dysfunction in familial epilepsy and demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1A alleles.
Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB).
These results illustrate that the clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy, and confirm the clinical experience that severe myoclonic epilepsy in infancy is the most severe form on this spectrum.