A new Chrna4 mutation with low penetrance in XXXX .

@entity26381 @entity72304 @entity1238 @entity535 @entity302 @entity4940 @entity934
PURPOSE: To identify and characterize the mutation(s) causing @entity4940 in a German extended family. METHODS: Neuronal nicotinic @entity934 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 @entity1238 oocytes. RESULTS: We report a new CHRNA4 mutation, causing a alpha4- @entity72304 @entity535 exchange at the extracellular end of the second transmembrane domain (TM). Functional studies of alpha4- @entity72304 revealed an increased ACh sensitivity of the mutated receptors. alpha4- @entity72304 is associated with an unusual low penetrance of the @entity302 phenotype. Sequencing of the @entity26381 -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 @entity302 are not always associated with an autosomal dominant mode of inheritance. alpha4- @entity72304 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.
