[en] Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Ronen, G.M., Rosales, T.O., Connolly, M., Anderson, V.E. & Leppert, M. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology 43, 1355-1360 (1993).
Plouin, P. Benign infantile neonatal convulsions in Idiopathic Generalized Epilepsies: Clinical, Experimental and Genetic Aspects (eds Malafosse, A. et al.) 39-44 (John Libbey, London, 1994).
Hauser, W.A. & Kurland, L.T. The epidemiology of epilepsy in Rochester, Minnesota. 1935 through 1967. Epilepsia 16, 1-66 (1975).
Leppert, M. et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature 337, 647-648 (1989).
Ryan, S.G. et al. Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. Ann. Neurol. 29, 469-473 (1991).
Malafosse, A. et al. Confirmation of linkage of benign familial neonatal convulsions to D20S19 and D20S20. Hum. Genet. 89, 54-58 (1992).
Steinlein, O., Fischer, C., Keil, R., Smigrodzki, R. & Vogel, F. D20S19, linked to low-voltage EEG, benign neonatal convulsions, and Fanconi anaemia, maps to a region of enhanced recombination and is localized between CpG islands. Hum. Mol. Genet. 1, 325-329 (1992).
Lewis, T.B., Leach, R.J., Ward, K., O'Connell, P. & Ryan, S.G. Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. Am. J. Hum. Genet. 53, 670-675 (1993).
Steinlein, O., Schuster, V., Fischer, C. & Haussler, M. Benign familial neonatal convulsions: confirmation of genetic heterogeneity and further evidence for a second locus on chromosome 8q. Hum. Genet. 95, 411-415 (1995).
Leppert, M. et al. Searching for human epilepsy genes: a progress report. Brain Pathol. 3, 357-369 (1993).
Wang, Q. et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genet 12, 17-23 (1996).
Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. Mol. Biol. 215, 403-410 (1990).
Neyroud, N. et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nature Genet. 15, 186-189 (1997).
Kozak, M. At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J. Mol. Biol. 196, 947-950 (1987).
Yokoyama, M., Nishi, Y., Yoshii, J., Okubo, K. & Matsubara, K. Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles. DNA Res. 3, 311-320 (1996).
Wei, A., Jegla, T. & Salkoff, L. Eight potassium channel families revealed by the C. elegans genome project. Neuropharmacology 35, 805-829 (1996).
Keating, M.T. & Sanguinetti, M.C. Pathophysiology of ion channel mutations. Curr. Opin. Genet. Dev. 6, 326-333 (1996).
Meldrum, B.S. Neurotransmission in epilepsy. Epilepsia 36, S30-S35 (1995).
McNamara, J.O. Cellular and molecular basis of epilepsy. J. Neurosci. 14, 3413-3425 (1994).
Sanguinetti, M.C. et al. Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel. Nature 384, 80-83 (1996).
Patil, N. et al. A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nature Genet. 11, 126-129 (1995).
Signorini, S., Liao, Y.J., Duncan, S.A., Jan, L.Y. & Stoffel, M. Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2. Proc. Natl. Acad. Sci. USA 94, 923-927 (1997).
Russell, M.W., Dick, M., II. Collins, F. S. & Brody, L.C. KVLQT1 mutations in three families with familial or sporadic long QT syndrome. Hum. Mol. Genet. 5, 1319-1324 (1996).
Yang, W.-P. et al. KVLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias. Proc. Natl. Acad. Sci. USA 94, 4017-4021 (1997).
Browne, D.L. et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nature Genet. 8, 136-140 (1994).
Chandy, K.G. & Gutman, G.A., Handbook of Receptors and Channels: Ligand and Voltage-Gated Ion Channels 1-71 (CRC, Ann Arbor, Michigan, 1995).
Jan, L.Y. & Jan, Y.N. Cloned potassium channels from eukaryotes and prokaryotes. Annu. Rev. Neurosci. 20, 91-123 (1997).
Lopez, G.A., Jan, Y.N. & Jan, L.Y. Evidence that the S6 segment of the Shaker voltage-gated K+ channel comprises part of the pore. Nature 367, 179-182 (1994).
Tytgat, J. Mutations in the P-region of a mammalian potassium channel (RCK1): a comparison with the Shaker potassium channel. Biochem. Biophys. Res. Commun. 203, 513-518 (1994).
Nakamura, R.L., Anderson, J.A. & Gaber R.F. Determination of key structural requirements of a K+ channel pore. J. Biol. Chem. 272, 1011-1118 (1997).
Heginbotham, L., Lu, Z., Abramson, T. & MacKinnon, R. Mutations in the K+ channel signature sequence. Biophys. J. 66, 1061-1067 (1994).
Hidalgo, P. & MacKinnon, R. Revealing the architecture of a K+ channel pore through murant cycles with a peptide inhibitor. Science 268, 307-310 (1995).
Guipponi, M. et al. Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q. Hum. Mol. Genet. 6, 473-477 (1997).
Vigevano, F. et al. Benign infantile familial convulsions in Idiopathic Generalized Epilepsies: Clinical, Experimental and Genetic Aspects (eds Malafosse, A. et al.) 45-49 (John Libbey, London, 1994).
Ptacek, L.J. Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromuscul. Disord. 7, 250-255 (1997).
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.