Health Conditions Related to Genetic Changes
Autosomal dominant nocturnal frontal lobe epilepsy
At least one mutation in the CHRNA2 gene has been found to cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). It appears that changes in this gene are a very rare cause of ADNFLE. Some researchers suspect that the known mutation actually causes a separate form of epilepsy with features similar to ADNFLE.
The identified CHRNA2 mutation changes a single protein building block (amino acid) in the α2 subunit of nAChR channels. Specifically, it replaces the amino acid isoleucine with the amino acid asparagine at protein position 279 (written as Ile279Asn or I279N). This mutation makes the channels more sensitive to the neurotransmitter acetylcholine, allowing them to open more easily than usual. The resulting increase in ion flow across the cell membrane alters the release of neurotransmitters, which changes signaling between neurons. Researchers believe that the overexcitement of certain neurons in the brain triggers the abnormal brain activity associated with seizures. It is unclear why the seizures seen in ADNFLE start in the frontal lobes of the brain and occur most often during sleep.
More About This Health ConditionOther Names for This Gene
- Acetylcholine receptor, neuronal nicotonic, alpha-2 subunit
- ACHA2_HUMAN
- Cholinergic receptor, neuronal nicotinic, alpha polypeptide 2
- cholinergic receptor, nicotinic alpha 2
- cholinergic receptor, nicotinic, alpha 2
- cholinergic receptor, nicotinic, alpha 2 (neuronal)
- cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D, Curia G, Cianchetti C, Pasqualetti M, Becchetti A, Guerrini R, Casari G. Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am J Hum Genet. 2006 Aug;79(2):342-50. doi: 10.1086/506459. Epub 2006 Jun 26. Citation on PubMed or Free article on PubMed Central
- Arneric SP, Holladay M, Williams M. Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem Pharmacol. 2007 Oct 15;74(8):1092-101. doi: 10.1016/j.bcp.2007.06.033. Epub 2007 Jun 26. Citation on PubMed
- Combi R, Ferini-Strambi L, Tenchini ML. CHRNA2 mutations are rare in the NFLE population: evaluation of a large cohort of Italian patients. Sleep Med. 2009 Jan;10(1):139-42. doi: 10.1016/j.sleep.2007.11.010. Epub 2008 Jan 28. Citation on PubMed
- Gu W, Bertrand D, Steinlein OK. A major role of the nicotinic acetylcholine receptor gene CHRNA2 in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is unlikely. Neurosci Lett. 2007 Jul 5;422(1):74-6. doi: 10.1016/j.neulet.2007.06.006. Epub 2007 Jun 8. Citation on PubMed
- Marini C, Guerrini R. The role of the nicotinic acetylcholine receptors in sleep-related epilepsy. Biochem Pharmacol. 2007 Oct 15;74(8):1308-14. doi: 10.1016/j.bcp.2007.06.030. Epub 2007 Jun 23. Citation on PubMed
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