Journal Article

An Insertion Mutation of the CHRNA4 Gene in a Family With Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

Ortrud K. Steinlein, Andres Magnusson, Jens Stoodt, Sonia Bertrand, Sigrid Weiland, Samuel F. Berkovic, Karl O. Nakken, Peter Propping and Daniel Bertrand

in Human Molecular Genetics

Volume 6, issue 6, pages 943-947
Published in print June 1997 | ISSN: 0964-6906
Published online June 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.6.943
An Insertion Mutation of the CHRNA4 Gene in a Family With Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

Show Summary Details

Preview

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 a4 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.

Journal Article.  3848 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.