This mutant displays increased affinity for acetylcholine faster desensitization compared to wild-type receptors.The most recently discovered mutation in CHRNA4 associated with ADNFLE is T265M, again located in the second transmembrane spanning segment. This mutation has been little studied and all that is known is that it produces receptors with increased sensitivity to acetylcholine and has a low penetrance. 15q24
Some families have been shown to not have mutations in CHRNA4 and, furthermore, to show no linkage around it. Instead some of these families show strong linkage on chromosome 15 (15q24) near CHRNA3, CHRNA5, and CHRNB4. Causative genes in this area are still unknown. CHRNB2
Three mutations have been found in the gene CHRNB2, which encodes an acetylcholine receptor β2 subunit. Two of these mutations, V287L and V287M, occur at the same amino acid, again in the second transmembrane spanning region. The V287L mutation results in receptors that desensitize at a much slower rate compared to wild-type. The V287M mutant displays a higher affinity for acetylcholine when compared to wild-type receptors. As with the mutations in CHRNA4, these mutants lead to receptors less sensitive to calcium.The other known mutation in CHRNB2 is I312M, located in the third membrane-spanning region. Receptors containing these mutant subunits display much larger currents and a higher sensitivity to acetylcholine than wild-type receptors. CHRNA2
Recently, the I279N mutation has been discovered in the first transmembrane spanning segment of CHRNA2, which encodes a nicotinic acetylcholine receptor α2 subunit similar to the nAChR α4 encoded by CHRNA4.
This mutant shows a higher sensitivity to acetylcholine and unchanged desensitization compared to wild-type. Diagnosis
Diagnosis is typically made upon patient history, although EEG recordings can be confirmatory if they occur during attacks. Management
Anti-epileptic drugs are normally used to combat ADNFLE. These drugs are discussed in the main epilepsy article. Footnotes
Further reading
GeneReviews/NCBI/NIH/UW entry on Autosomal Dominant Nocturnal Frontal Lobe Epilepsy


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