FEBS Letters
Volume 583, Issue 10 , Pages 1599-1604, 19 May 2009

Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene

Edited by Maurice Montal

  • Jean-Charles Hoda

      Affiliations

    • Department of Neuroscience, Medical Faculty, Geneva, Switzerland
    • ,
  • Mario Wanischeck

      Affiliations

    • Institute of Human Genetics, University Hospital, Ludwig Maximilians University Munich, Goethestr. 29, 80336 Munich, Germany
    • ,
  • Daniel Bertrand

      Affiliations

    • Department of Neuroscience, Medical Faculty, Geneva, Switzerland
    • ,
  • Ortrud K. Steinlein

      Affiliations

    • Institute of Human Genetics, University Hospital, Ludwig Maximilians University Munich, Goethestr. 29, 80336 Munich, Germany
    • Corresponding Author InformationCorresponding author. Fax: +49 89 5160 4468.

Received 27 February 2009; received in revised form 31 March 2009; accepted 14 April 2009. published online 20 April 2009.

Abstract 

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) can be caused by mutations in the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes CHRNA4 and CHRNB2. Recently, a point mutation (α2-I279N) associated with sleep-related epilepsy has been described in a third nAChR gene, CHRNA2. We demonstrate here that α2-I279N can be co-expressed with the major structural subunit CHRNB2. α2-I279N causes a marked gain-of-function effect and displays a distinct biopharmacological profile, including markedly reduced inhibition by carbamazepine and increased nicotine sensitivity.

Abbreviations: ADNFLE, autosomal dominant nocturnal frontal lobe epilepsy, nAChR, nicotinic acetylcholine receptor, PCR, polymerase chain reaction, Ach, acetylcholine

Keywords: Frontal lobe epilepsy, Nicotinic acetylcholine receptor, CHRNA2 protein, human, CHRNA4 protein, human

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PII: S0014-5793(09)00302-0

doi:10.1016/j.febslet.2009.04.024

FEBS Letters
Volume 583, Issue 10 , Pages 1599-1604, 19 May 2009

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