Mutational analysis of CACNA1G in idiopathic generalized epilepsy. Mutation in brief #962. Online.
Recent studies have strongly implicated low voltage-activated/T-type calcium channels (T-channels) in the etiology of epilepsy. Here, we report the results of a mutational analysis of the CACNA1G gene, encoding the T-channel Ca(V)3.1/(1G) subunit, using a cohort of 123 mostly Japanese and Hispanic patients with idiopathic generalized epilepsies (IGE) and 360 healthy control individuals. We found 13 variants, including five which involved amino acid substitutions. One variant, c.1709C>T (Ala570Val), is present in a sporadic case of juvenile myoclonic epilepsy (JME) with early childhood absence and astatic seizures, but was not found in control samples. Another variant, c.3265G>T (Ala1089Ser), was observed in three family members affected with JME, and also in one control individual. Two JME patients and three control individuals harbored a third variant, c.2968G>A (Asp980Asn). Although not statistically significant, slightly faster inactivation decay rates were observed in some mutant channels. Our collective findings flag CACNA1G as a potential susceptibility locus for IGE subsyndromes that warrants closer investigation.
Singh
Baljinder
B
Laboratory for Neurogenetics, RIKEN Brain Science Institute, Saitama, Japan.
Monteil
Arnaud
A
Bidaud
Isabelle
I
Sugimoto
Yoshihisa
Y
Suzuki
Toshimitsu
T
Hamano
Shin-ichiro
S
Oguni
Hirokazu
H
Osawa
Makiko
M
Alonso
Maria E
ME
Delgado-Escueta
Antonio V
AV
Inoue
Yushi
Y
Yasui-Furukori
Norio
N
Kaneko
Sunao
S
Lory
Philippe
P
Yamakawa
Kazuhiro
K
D020747:Calcium Channels, T-Type; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D009154:Mutation
C121855:CACNA1G protein, human; D020747:Calcium Channels, T-Type