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Link to original content: https://doi.org/10.1038/ng0198-53
A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family | Nature Genetics
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A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family

Nature Genetics volume 18, pages 53–55 (1998)Cite this article

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 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.

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Authors and Affiliations

  1. Department of Human Genetics, University of Utah, Salt Lake City, Utah, 84112, USA

    Carole Charlier, Nanda A. Singh & Mark Leppert

  2. Department ofPediatric Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Stephen G. Ryan

  3. Department of Medical Genetics, Indiana University School of Medicine Indianapolis, Indiana, 46902, USA

    Tracey B. Lewis

  4. Department of Cellular & Structural Biology, University of Texas Health Sciences Center, San Antonio, Texas, 78284, USA

    Bonnie E. Reus & Robin J. Leach

Authors
  1. Carole Charlier
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  2. Nanda A. Singh
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  5. Bonnie E. Reus
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  7. Mark Leppert
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Correspondence to Mark Leppert.

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Charlier, C., Singh, N., Ryan, S. et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 18, 53–55 (1998). https://doi.org/10.1038/ng0198-53

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