A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions.
BACKGROUND
The underlying genetic abnormalities of rare familial idiopathic epilepsy have been identified, such as mutation in KCNQ2, a K(+) channel gene. Yet, few genetic abnormalities have been reported for commoner epilepsy, i.e., sporadic idiopathic epilepsy, which share a phenotype similar to those of familial epilepsy.


OBJECTIVE
To search for the genetic cause of seizures in a girl with the diagnosis of non-familial benign neonatal convulsions, and define the consequence of the genetic abnormality identified.


METHODS
Genetic abnormality was explored within candidate genes for benign familial neonatal and infantile convulsions, such as KCNQ2, 3, 5, KCNE2, SCN1A and SCN2A. The electrophysiological properties of the channels harboring the identified mutation were examined. Western blotting and immunostaining were employed to characterize the expression and intracellular localization of the mutant channel molecules.


RESULTS
A novel heterozygous mutation (c.910-2delTTC or TTT, Phe304del) of KCNQ2 was identified in the patient. The mutation was de novo verified by parentage analysis. The mutation was associated with impaired functions of KCNQ K(+) channel. The mutant channels were expressed on the cell surface.


CONCLUSIONS
The mutant Phe304del of KCNQ2 leads to null function of the KCNQ K(+) channel but the mutation does not alter proper channel sorting onto the cell membrane. Our findings indicate that the genes responsible for rare inherited forms of idiopathic epilepsy could be also involved in sporadic forms of idiopathic epilepsy and expand our notion of the involvement of molecular mechanisms in the more common forms of idiopathic epilepsy.
Ishii
Atsushi
A
Department of Pediatrics, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Fukuma
Goryu
G
Uehara
Akira
A
Miyajima
Tasuku
T
Makita
Yoshio
Y
Hamachi
Akiyo
A
Yasukochi
Midori
M
Inoue
Takahito
T
Yasumoto
Sawa
S
Okada
Motohiro
M
Kaneko
Sunao
S
Mitsudome
Akihisa
A
Hirose
Shinichi
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis / Q000379:methods; D004569:Electroencephalography; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D051658:KCNQ2 Potassium Channel