Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome.
Mutations of the gene encoding the alpha2 subunit of the neuronal sodium channel, SCN2A, have been found in benign familial neonatal-infantile seizures (BFNIS). In Dravet syndrome, only one nonsense mutation of SCN2A was identified, while hundreds of mutations were found in the paralogue gene, SCN1A, which encodes the alpha1 subunit. This study examines whether SCN2A mutations are associated with Dravet syndrome. We screened for mutations of SCN1A, SCN2A and GABRG2 (the gene encoding gamma2 subunit of the GABA(A) receptor) in 59 patients with Dravet syndrome and found 29 SCN1A mutations and three missense SCN2A mutations. Among the three, one de novo SCN2A mutation (c.3935G>C: R1312T) identified in a patient was thought to affect an arginine residue in a voltage sensor of the channel and hence, to be pathogenic. This finding suggests that both nonsense mutations and missense SCN2A mutations cause Dravet syndrome.
Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Xiuyu
X
Shi
Sawa
S
Yasumoto
Eiji
E
Nakagawa
Tatsuya
T
Fukasawa
Satoshi
S
Uchiya
Shinichi
S
Hirose
D018389:Codon, Nonsense / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D020125:Mutation, Missense / Q000235:genetics*; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
D018389:Codon, Nonsense; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; D015222:Sodium Channels