A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family

• Published in: Nature genetics Vol. 18; no. 1; pp. 53 - 55
• Main Authors: Charlier, Carole, Singh, Nanda A., Ryan, Stephen G., Lewis, Tracey B., Reus, Bonnie E., Leach, Robin J., Leppert, Mark
• Format: Journal Article Web Resource
• Language: English
• Published: New York Nature Publishing Group US 01.01.1998; Nature Publishing Group
• Subjects: Agriculture; Amino Acid Sequence; Animal Genetics and Genomics; Base Sequence; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromosomes, Human, Pair 8; Epilepsy, Generalized - genetics; Female; Gene Function; Genetic Variation; Genetics & genetic processes; Génétique & processus génétiques; Human Genetics; Humans; KCNQ3 Potassium Channel; letter; Life sciences; Male; Molecular Sequence Data; Mutation; Pedigree; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Potassium Channels - genetics; Potassium Channels, Voltage-Gated; Sciences du vivant; Sequence Homology, Amino Acid
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng0198-53

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 observed4. 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 family10. Here we describe an additional member, KCNQ3. We mapped this new gene to chromosome 8, between markers D8S256 and D8S284 on a radiation hybrid map11. We screened KCNQ3 for mutations in the large BFNC family4'7 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 patient12. KCNQ2, KCNQ3 and undiscovered genes of the same family of K+ channels are strong candidates for other IGEs.