CHRNA7 was first reported as a candidate gene for autosomal dominant epilepsy (MONDO:0005027) in 2002 (PMID: 12049804) due to its presence within recurrent 15q13.3 copy number variants, which have been reported to increase the risk of idiopathic generalized epilepsy (PMID:19136953). Since this publication, most reported probands have had microdeletions and microduplications in the 15q13.3 region, which often includes at least six other genes (ARHGAP11B, MTMR15, MTMR10, TRPM1, KLF13, and OTUD7A). Because these deletions are not isolated to CHRNA7 alone, they are not included in this curation.
Three missense variants that have been reported in three probands in one paper were evaluated as a part of this curation (PMID: 26421493). However, none of these cases were awarded points, as their variants were either inherited from a healthy parent, or were predicted to be benign. Another paper with a homozygous CHRNA7 knock-out mouse model found no evidence of recapitulating phenotypes observed in humans, and there were no electrophysiological phenotypic differences between the wild type and knock-out mice (PMID: 28045139). Taken together, the evidence supporting the relationship between CHRNA7 and autosomal dominant epilepsy has been REFUTED and no valid evidence remains to support the claim. This classification has been approved by the ClinGen Epilepsy GCEP on February 7th, 2023 (SOP Version 9).
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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