Mutations of the neuronal nicotinic acetylcholine receptors and their association with ADNFLE

Neurophysiol Clin. 2002 Apr;32(2):99-107. doi: 10.1016/s0987-7053(02)00294-0.


Elucidating the origin of epileptic seizures represents one of the many ways by which today's scientists are approaching this devastating neurological disorder. Although epilepsies have several different origins ranging from head trauma to genetically transmissible affections, common neuronal network dysfunction can be recognised between these many forms of the disease. Thus, understanding the basic mechanisms underlying some genetically transmissible epilepsies should bring new and important knowledge that is readily applicable to other types of epilepsies. In this work we review our current knowledge of one genetically transmissible form of nocturnal epilepsy, the ADNFLE. In the light of the most recent findings obtained on five mutants of the neuronal nicotinic acetylcholine receptors associated with ADNFLE, we discuss the effects of these spontaneous genome alterations on the receptor function. The only common trait identified so far between these mutant receptors is an increase in acetylcholine sensitivity. Based on our understanding of the receptor distribution in the different brain areas, their development and the neuronal network circuitry, we hypothesise that increased acetylcholine sensitivity causes an unbalance in the fine tuning of the cortico-reticular thalamic and thalamo-cortical loops. In addition, we illustrate how spontaneous mutations in the gene coding for a receptor provoke a change in its pharmacological profile and thereby might account for the inter-individual therapeutic sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epilepsy, Frontal Lobe / genetics*
  • Humans
  • Mutation / genetics*
  • Neurons / drug effects
  • Neurons / metabolism
  • Receptors, Nicotinic / genetics*


  • Receptors, Nicotinic