Abstracts

Rationale: Mutations in the neuronal voltage-gated sodium channel ?1-subunit gene (SCN1A) have been identified in many patients with phenotypes within the generalized epilepsy with febrile seizures plus (GEFS ) spectrum. In addition, the International League Against Epilepsy Genetics Commission indicates that genetic testing for SCN1A mutations is one of most clinically useful among the tests for genes that influence risk for developing epilepsy (Ottman et al. 2010). The aim of this study is to search for mutations in the SCN1A gene in patients with severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and myoclonic astatic epilepsy (MAE or Doose syndrome), both within the GEFS spectrum, and to establish genotype-phenotype correlations. Methods: We performed mutation screening in the SCN1A gene in nine patients with SMEI and 12 with MAE. Prediction algorithms were used to analyze the possible impact of the amino-acid changes in the protein function. In addition, multiplex ligation-dependent probe amplification (MLPA) is being used to detect copy number variations within SCN1A. Results: Mutation analysis revealed six potentially deleterious variants only in patients with SMEI: three missense mutations (c.829T>C, c.971A>C and c.5434T>C) that lead to amino-acid residue substitutions and are predicted to affect protein function, an insertion (c.3719_3720insGATA) that promotes a frameshift and two splice donor site mutations (IVS4 1G>A and IVS8 3G>T). To date, preliminary MLPA analysis shows no abnormalities. Conclusions: Since potentially deleterious variants were found only in patients with the most severe phenotype, our results indicate that molecular testing for clinical purposes seems to yield best results in patients with SMEI. According to our results, the main clinical feature associated with deleterious mutations in SCN1A was the occurrence of seizures with low fever (37.5-38 C), which was present in all patients with SCN1A mutations in our study.