Variants in the CHRNA2 gene has been reported in 18 affected individuals with autosomal dominant nocturnal frontal lobe epilepsy since 2006 (Aridon et al.). Three unique missense variant proved to affect the protein function by patch clamp analysis (Aridon et al., Conti et al., Vila et al.). The variant in this gene was identified by linkage analysis followed by Sanger sequencing, and segregated with disease in 9 additional family members. In summary, there is limited evidence to support the CHRNA2 and nocturnal frontal lobe epilepsy association. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel by 1/7/2020.
Lumping and Splitting: Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in phenotypic variability between three disease entities: (1) Nocturnal frontal lobe epilepsy (MONDO:0000030), (2) Idiopathic epilepsy (MONDO:0005579) and (3) Benign familial infantile seizure (MONDO:0011140). Therefore, we have split curations for the disease entities, (1) Nocturnal frontal lobe epilepsy (MONDO:0000030), (2) Idiopathic epilepsy (MONDO:0005579) and (3) Benign familial infantile seizure (MONDO:0011140).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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