title: KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum.
abstract: Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant generalized epilepsy of the newborn infant. Seizures occur repeatedly in the first days of life and remit by approximately 4 months of age. Previously our laboratory cloned two novel potassium channel genes, KCNQ2 and KCNQ3, and showed that they are mutated in patients with BFNC. In this report, we characterize the breakpoints of a previously reported interstitial deletion in the KCNQ2 gene and show that only KCNQ2 is deleted. We identify 11 novel mutations in KCNQ2 and one novel mutation in the KCNQ3 potassium channel genes. In one family, the phenotype extends beyond neonatal seizures and includes rolandic seizures, and a subset of families has onset of seizures in infancy. In the Xenopus oocyte expression system, we characterize five KCNQ2 and one KCNQ3 disease-causing mutations. These mutations cause a variable loss of function, and selective effects on the biophysical properties of KCNQ2/KCNQ3 heteromultimeric channels. We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. nandas@genetics.utah.edu
authors.forename: Nanda A
authors.initials: NA
authors.lastname: Singh
authors.forename: Peter
authors.initials: P
authors.lastname: Westenskow
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
authors.forename: Chris
authors.initials: C
authors.lastname: Pappas
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leslie
authors.forename: Jessica
authors.initials: J
authors.lastname: Dillon
authors.forename: V Elving
authors.initials: VE
authors.lastname: Anderson
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sanguinetti
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis / Q000379:methods; D020936:Epilepsy, Benign Neonatal / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary / Q000235:genetics; D014158:Transcription, Genetic; D014982:Xenopus laevis
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary