Neuronal sodium-channel alpha 1-subunit mutations in generalized epilepsy with febrile seizures plus

Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epile psy syndrome characterized by the presence of febrile and afebrile seizures . The first gene, GEFS1, was mapped to chromosome 19q and was identified as the sodium-channel beta1-subunit, SCN1B. A second locus on chromosome 2q, GEFS2, was recently identified as the sodium-channel alpha1-subunit, SCN1A. Single-stranded conformation analysis (SSCA) of SCN1A was performed in 53 unrelated index cases to estimate the frequency of mutations in patients wi th GEFS+. No mutations were found in 17 isolated cases of GEFS+. Three nove l SCN1A mutations-D188V, V1353L, and I1656M-were found in 36 familial cases ; of the remaining 33 families, 3 had mutations in SCN1B. On the basis of S SCA, the combined frequency of SCN1A and SCN1B mutations in familial cases of GEFS+ was found to be 17%.