Human Molecular Genetics, Vol 6, 943-947, Copyright © 1997 by Oxford University Press
OK Steinlein, A Magnusson, J Stoodt, S Bertrand, S Weiland, SF Berkovic, KO Nakken, P Propping and D Bertrand
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first,
and to date only, idiopathic epilepsy for which a specific mutation has
been found. A missense mutation in the critical M2 domain of the alpha4
subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) has been
recently identified in one large Australian pedigree. Here we describe a
novel mutation in the M2 domain of the CHRNA4 gene in a Norwegian family.
Three nucleotides (GCT) were inserted at nucleotide position 776 into the
coding region for the C-terminal end of the M2 domain. Physiological
investigations of the receptor reconstituted with the mutated CHRNA4
subunit reveal that this insertion does not prevent the receptor function
but increases its apparent affinity for ACh. In addition, this mutant
receptor shows a significantly lower calcium permeability that, at the
cellular level, may correspond to a loss of function. Comparison of the two
mutations identified so far in families with ADNFLE illustrates that
different mutations can result in similar phenotypes.
ARTICLES
An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy
Institute for Human Genetics, University of Bonn, Germany. human@snphysio2.wilhelm.uni-bonn.de
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