Submission Details

Autosomal dominant

06/03/2019

The CHRNA2 gene is located on chromosome 8 at 8p21.2 and encodes the cholinergic receptor nicotinic alpha 2 subunit. CHRNA2 is expressed in the brain and is involved with the binding of acetylcholine and the opening of an ion-conducting channel across the plasma membrane (20016990: Steinlein and Bertrand 2010; 25717303: Becchetti et al. 2015). The CHRNA2 gene was first reported in association with autosomal dominant epilepsy, nocturnal frontal lobe, in 2006 (16826524: Aridon et al. 2006). At least four unique variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Heterozygous missense variants in this gene have been reported in at least four probands from four publications (16826524: Aridon et al. 2006; 25770198: Conti et al. 2015; 25847220: Trivisano et al. 2015; 30809122: Villa et al. 2019). All reported variants were inherited, and variants in this gene segregated with disease in approximately 20 additional family members. A disease mechanism has not been established; two of the identified variants resulted in a loss of receptor function, while a third resulted in increased receptor sensitivity. This association is also supported by expression data, in vitro functional assays, and a shared biochemical function other nicotinic acetylcholine receptor subunit genes (20016990: Steinlein and Bertrand 2010; 16826524: Aridon et al. 2006). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.

16826524 25770198 25847220 30809122 20016990 16826524