Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified.
BACKGROUND
Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) 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).


METHODS
Clinical characterization and molecular genetic analysis of a cohort of patients.


METHODS
University hospitals, rehabilitation centers, and molecular biology laboratories.


METHODS
Sixty unrelated patients with cryptogenic epileptic syndromes.


METHODS
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.
Zucca
Claudio
C
Clinical Neurophysiology Unit, E. Medea Scientific Institute, Lecco, Italy.
Redaelli
Francesca
F
Epifanio
Roberta
R
Zanotta
Nicoletta
N
Romeo
Antonino
A
Lodi
Monica
M
Veggiotti
Pierangelo
P
Airoldi
Giovanni
G
Panzeri
Chris
C
Romaniello
Romina
R
De Polo
Gianni
G
Bonanni
Paolo
P
Cardinali
Simonetta
S
Baschirotto
Cinzia
C
Martorell
Loreto
L
Borgatti
Renato
R
Bresolin
Nereo
N
Bassi
Maria Teresa
MT
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels