A potassium channel mutation in neonatal human epilepsy.
Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.
Biervert
C
C
Institute for Human Genetics, University of Bonn, Bonn, Germany.
Schroeder
B C
BC
Kubisch
C
C
Berkovic
S F
SF
Propping
P
P
Jentsch
T J
TJ
Steinlein
O K
OK
D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D003001:Cloning, Molecular; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009865:Oocytes / Q000378:metabolism; D016366:Open Reading Frames; D010375:Pedigree; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D014982:Xenopus laevis
D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D011188:Potassium