CHRNB2 was first reported in relation to autosomal dominant sleep-related hypermotor epilepsy in 2000 (De Fusco et al., PMID: 11062464). This disorder was previously referred to as nocturnal frontal lobe epilpeys. It is characterized by hypermotor seizures that occur most often in sleep and are occassionally associated with intellectual disability or psychiatric disorders.
At least 8 missense variants that have been reported in 12 probands in 10 publications (PMIDs: 27054081, 33391346, 35177946, 21497487, 18534914, 18456869, 17900292, 15964197, 11104662, 11062464) are included in this curation. The mechanism of pathogenicity appears to be gain-of-function.
This gene-disease association is also supported by experimental evidence, including spontaneous seizures during sleep in a rat model and a mouse model, as well as protein-protein interactions with CHRNA4 to form functional nicotinic acetylcholine receptor (nAChR) channels (PMIDs: 26091610, 19153075, 12944511).
In summary, there is a definitive relationship between CHRNB2 and autosomal dominant sleep-related hypermotor epilepsy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on February 7th, 2023. As of May 5th, 2023, this record underwent administrative updates in which the disease term in the evidence summary was revised to align with the updated Mondo disease term. No new evidence has been reviewed or added.
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).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.