Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome.

Abstract

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.

• Authors: Xiuyu Shi, Sawa Yasumoto, Eiji Nakagawa, Tatsuya Fukasawa, Satoshi Uchiya, Shinichi Hirose
• Journal: Brain & development (Brain Dev) Vol. 31 Issue 10 Pg. 758-62 (Nov 2009) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 19783390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• NAV1.2 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins
• SCN2A protein, human
• Sodium Channels

Topics

• Codon, Nonsense (genetics)
• Epilepsies, Myoclonic (genetics)
• Genetic Testing
• Humans
• Infant
• Mutation, Missense (genetics)
• NAV1.2 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins (genetics)
• Sodium Channels (genetics)