A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.
Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.
Singh
N A
NA
Department of Human Genetics, University of Utah, Salt Lake City 84112, USA.
Charlier
C
C
Stauffer
D
D
DuPont
B R
BR
Leach
R J
RJ
Melis
R
R
Ronen
G M
GM
Bjerre
I
I
Quattlebaum
T
T
Murphy
J V
JV
McHarg
M L
ML
Gagnon
D
D
Rosales
T O
TO
Peiffer
A
A
Anderson
V E
VE
Leppert
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002461:Cell Line, Transformed; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20; D018076:DNA, Complementary; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated