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Epilepsia. 2003 Jul;44(7):981-5.

A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy.

Author information

  • 1Department of Neurology, University of Essen, Essen, Germany.

Abstract

PURPOSE:

To identify and characterize the mutation(s) causing nocturnal frontal lobe epilepsy in a German extended family.

METHODS:

Neuronal nicotinic acetylcholine receptor (nAChR) subunit genes were screened by direct sequencing. Once a CHRNA4 mutation was identified, its biophysical and pharmacologic properties were characterized by expression experiments in Xenopus oocytes.

RESULTS:

We report a new CHRNA4 mutation, causing a alpha4-T265I amino acid exchange at the extracellular end of the second transmembrane domain (TM). Functional studies of alpha4-T265I revealed an increased ACh sensitivity of the mutated receptors. alpha4-T265I is associated with an unusual low penetrance of the epilepsy phenotype. Sequencing of the TM1-TM3 parts of the 1 known nAChR subunits did not support a two-locus model involving a second nAChR sequence variation.

CONCLUSIONS:

nAChR mutations found in familial epilepsy are not always associated with an autosomal dominant mode of inheritance. alpha4-T265I is the first nAChR allele showing a markedly reduced penetrance consistent with a major gene effect. The low penetrance of the mutation is probably caused by unknown genetic or environmental factors or both.

PMID:
12823585
[PubMed - indexed for MEDLINE]
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