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

Carole Charlier, Nanda A. Singh, Stephen G. Ryan, Tracey B. Lewis, Bonnie E. Reus, Robin J. Leach, Mark Leppert

Research output: Contribution to journalArticle

779 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)53-55
Number of pages3
JournalNature Genetics
Volume18
Issue number1
DOIs
StatePublished - Jan 20 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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