Abstract
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 language | English |
|---|---|
| Pages (from-to) | 489-494 |
| Number of pages | 6 |
| Journal | Archives of Neurology |
| Volume | 65 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2008 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Cryptogenic epileptic syndromes related to SCN1A : Twelve novel mutations identified. / Zucca, Claudio; Redaelli, Francesca; Epifanio, Roberta; Zanotta, Nicoletta; Romeo, Antonino; Lodi, Monica; Veggiotti, Pierangelo; Airoldi, Giovanni; Panzeri, Chris; Romaniello, Romina; De Polo, Gianni; Bonanni, Paolo; Cardinali, Simonetta; Baschirotto, Cinzia; Martorell, Loreto; Borgatti, Renato; Bresolin, Nereo; Bassi, Maria Teresa.
In: Archives of Neurology, Vol. 65, No. 4, 04.2008, p. 489-494.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cryptogenic epileptic syndromes related to SCN1A
T2 - Twelve novel mutations identified
AU - Zucca, Claudio
AU - Redaelli, Francesca
AU - Epifanio, Roberta
AU - Zanotta, Nicoletta
AU - Romeo, Antonino
AU - Lodi, Monica
AU - Veggiotti, Pierangelo
AU - Airoldi, Giovanni
AU - Panzeri, Chris
AU - Romaniello, Romina
AU - De Polo, Gianni
AU - Bonanni, Paolo
AU - Cardinali, Simonetta
AU - Baschirotto, Cinzia
AU - Martorell, Loreto
AU - Borgatti, Renato
AU - Bresolin, Nereo
AU - Bassi, Maria Teresa
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42249096976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42249096976&partnerID=8YFLogxK
U2 - 10.1001/archneur.65.4.489
DO - 10.1001/archneur.65.4.489
M3 - Article
C2 - 18413471
AN - SCOPUS:42249096976
VL - 65
SP - 489
EP - 494
JO - Archives of Neurology
JF - Archives of Neurology
SN - 0003-9942
IS - 4
ER -