Purpose: The sodium channel α1 subunit (SCN1A) gene is associated with febrile seizures (FS)-related epilepsies.The mutation types of SCN1A, such as truncation, splice-site and missense mutations, are important determinants of phenotypes.In contrast to truncation or missense mutations in which the resulting protein abnormalities are known, the consequences of splice-site mutations in SCN1A are not studied.It is also considered whether mutations adjacent to splice-site may affect splicing and are associated with epilepsy.Methods: Mutations in SCN1A were screened by PCR amplification and denaturing high performance liquid chromatography (DHPLC) analysis and direct sequencing in patients with epilepsy and FS.In vitro minigene splicing assay was applied to investigate the consequences of 11 mutations at or adjacent to splice-sites of SCN1A.Results: Three mutations in invariant splice junction caused exon or partial exon skipping, including mutations c.602+1G>A, c.3705+1G>T and c.4284+2T>C that caused skipping of exon 4, partial skipping of exon 18 (49 bp) and skipping of exon 21, respectively.The associated phenotype was Dravet syndrome.Mutation c.473+5G>A generated two aberrant transcripts, partial exon 3 skipping and exon 3 plus partial exon 2 skipping.Two patients with this mutation had FS+ or partial epilepsy and FS+ (PEFS+).Two mutations in introns that are more away from the splice sites, including c.473+ 110A>G and c.4853-25T>A, generated aberrant transcripts as well as normal transcripts.The aberrant transcripts included one with intron 3 retained and another with a 26 bp-intron sequence retained.The phenotypes associated with these two mutations were PEFS+.In contrast, no aberrant transcripts were detected in mutations that are located in exon and are adjacent to splice-sites of SCN1A.Conclusion; This is the first report showing the consequences of SCN1A splice-site mutations in epilepsy patients.The severity of epilepsy is correlated with aberrant splicing level, which depends on the location of mutations.