Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy.
Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.
Kearney
Jennifer A
JA
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Wiste
Anna K
AK
Stephani
Ulrich
U
Trudeau
Michelle M
MM
Siegel
Anne
A
RamachandranNair
Rajesh
R
Elterman
Roy D
RD
Muhle
Hiltrud
H
Reinsdorf
Juliane
J
Shields
W Donald
WD
Meisler
Miriam H
MH
Escayg
Andrew
A
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels