The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation.
By mutation screening of the SCN1A gene, we identified for the first time a case of two missense mutations in cis (p.[Arg1525Gln;Thr297Ile]) in all affected individuals of an Italian family showing GEFS+ and idiopathic generalized epilepsy (IGE).
SCN1A mutation may be a clinically-useful genetic marker in order to distinguish GEFS+ patients from those with classic idiopathic generalised epilepsy, even if they present an atypical clinical picture.
A genome-wide association study in idiopathic generalized epilepsy revealed the first common risk variants for human seizure disorders including variants in VRK2, PNPO and SCN1A.
Although a few candidate disease alleles were identified, the patient survey suggests that SCN1A is not a major contributor to idiopathic generalized epilepsy.