Cryptogenic epileptic syndromes related to SCN1A: Twelve novel mutations identified

Claudio Zucca, Francesca Redaelli, Roberta Epifanio, Nicoletta Zanotta, Antonino Romeo, Monica Lodi, Pierangelo Veggiotti, Giovanni Airoldi, Chris Panzeri, Romina Romaniello, Gianni De Polo, Paolo Bonanni, Simonetta Cardinali, Cinzia Baschirotto, Loreto Martorell, Renato Borgatti, Nereo Bresolin, Maria Teresa Bassi

Research output: Contribution to journalArticlepeer-review


Background: Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel α 1 subunit (Nav1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy. Objective: To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause). Design: Clinical characterization and molecular genetic analysis of a cohort of patients. Setting: University hospitals, rehabilitation centers, and molecular biology laboratories. Patients: Sixty unrelated patients with cryptogenic epileptic syndromes. Main Outcome Measures: Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening. Results: No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative. Conclusions: These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies.

Original languageEnglish
Pages (from-to)489-494
Number of pages6
JournalArchives of Neurology
Issue number4
Publication statusPublished - Apr 2008

ASJC Scopus subject areas

  • Neuroscience(all)


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