Abstracts

Mutations in [italic]SCN1A[/italic] are associated with many epilepsy syndromes such as severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in [italic]SCN2A2[/italic] have been described in benign familial neonatal-infantile seizures and GEFS+ but to date only one [italic]SCN2A2[/italic] mutation has been associated with intractable epilepsy. We evaluated the contribution of [italic]SCN1A[/italic] and [italic]SCN2A2[/italic] mutations to infantile onset intractable epilepsy in Finnish patients., [italic]SCN1A[/italic] and [italic]SCN2A2[/italic] were screened for mutations in 33 patients, 21 of which had a clinical suspicion of SMEI. We amplified all exons and exon-intron boundaries of [italic]SCN1A[/italic] and [italic]SCN2A2[/italic] from genomic DNA and sequenced the PCR products with an ABI 3730 DNA Analyzer. Sequences were analyzed using the Sequencher 4.5 program., We found six different [italic]de novo[/italic] mutations in [italic]SCN1A[/italic]: One nonsense, two splice site, one frameshift-causing and two missense mutations that change highly conserved amino acids. Two of the mutations were previously described. The clinical presentation in three of the mutation positive patients is SMEI. Two patients have borderline SMEI and one has a milder phenotype with normal cognitive development. We also found one previously undescribed [italic]de novo[/italic] missense mutation of a conserved amino acid in [italic]SCN2A2[/italic] in a patient with infantile onset epilepsy and episodic ataxia. None of the mutations were observed in 192 control chromosomes., Our findings are compatible with previous findings showing that [italic]de novo SCN1A[/italic] mutations are a major cause of SMEI. [italic]SCN2A2[/italic] mutations are found only in a small subset of infantile onset intractable epilepsy.,