title: A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.
abstract: Epileptic disorders affect about 20-40 million people worldwide, and 40% of these are idiopathic generalized epilepsies (IGEs; ref. 1). Most of the IGEs that are inherited are complex, multigenic diseases. To address basic mechanisms for epilepsies, we have focused on one well-defined class of IGEs with an autosomal-dominant mode of inheritance: the benign familial neonatal convulsions (BFNC; refs 2,3). Genetic heterogeneity of BFNC has been observed. Two loci, EBN1 and EBN2, have been mapped by linkage analysis to chromosome 20q13 (refs 5,6) and chromosome 8q24 (refs 7,8), respectively. By positional cloning, we recently identified the gene for EBN1 as KCNQ2 (ref. 9). This gene, a voltage-gated potassium channel, based on homology, is a member of the KQT-like family. Here we describe an additional member, KCNQ3. We mapped this new gene to chromosome 8, between markers D8S256 and D8S284 on a radiation hybrid map. We screened KCNQ3 for mutations in the large BFNC family previously linked to chromosome 8q24 in the same marker interval. We found a missense mutation in the critical pore region in perfect co-segregation with the BFNC phenotype. The same conserved amino acid is also mutated in KVLQT1 (KCNQ1) in an LQT patient. KCNQ2, KCNQ3 and undiscovered genes of the same family of K+ channels are strong candidates for other IGEs.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City 84112, USA.
authors.forename: C
authors.initials: C
authors.lastname: Charlier
authors.forename: N A
authors.initials: NA
authors.lastname: Singh
authors.forename: S G
authors.initials: SG
authors.lastname: Ryan
authors.forename: T B
authors.initials: TB
authors.lastname: Lewis
authors.forename: B E
authors.initials: BE
authors.lastname: Reus
authors.forename: R J
authors.initials: RJ
authors.lastname: Leach
authors.forename: M
authors.initials: M
authors.lastname: Leppert
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002898:Chromosomes, Human, Pair 8; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D051659:KCNQ3 Potassium Channel; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017386:Sequence Homology, Amino Acid
chemical_list: D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated