Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy. (3rd April 2015)

• Record Type: Journal Article
• Authors: Trivisano, Marina; Terracciano, Alessandra; Milano, Teresa; Cappelletti, Simona; Pietrafusa, Nicola; Bertini, Enrico Silvio; Vigevano, Federico; Specchio, Nicola
• Is Part Of: Epilepsia. Volume 56:issue 5(2015:May)
• Page Start: e53
• Page End: e57
• Publication Date: 2015-04-03
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12967
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12967-abs-0001"> <title>Summary</title> <p>Nicotinic acetylcholine receptor genes are involved mainly in nocturnal frontal epilepsy. Despite extensive studies, to date, the α2 subunit did not show a strong association with this peculiar epileptic phenotype. We report <italic>CHRNA2</italic> missense mutation in a family with benign familial infantile seizures (BFIS). TrueSeq Custom Amplicon (TSCA) sequencing approach was used to screen 10 ion channel genes in patients with idiopathic epilepsies. TSCA revealed a heterozygous single‐nucleotide substitution in <italic>CHRNA2</italic> gene (c.1126 C>T; p. Arg376Trp) that segregated in a family with BFIS; based on bio‐informatics inspection, the change was predicted to be pathogenic. The investigated family includes parents and their three daughters. In affected individuals, seizures started between 6 and 24 months of age. Seizures were mainly in cluster and well‐controlled. Outcome was good in all subjects. Even if nicotinic acetylcholine receptor genes are traditionally associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), this single‐family description can open new possibilities in the genetic diagnosis, molecular characterization, and management of <italic>CHRNA2</italic>‐related epilepsy. The pathogenic conversion of arginine 376 to tryptophan alters all of these interactions in the cytoplasmic domain, never reported to be involved in epileptogenic mechanism. Further functional tests will be necessary to strongly relate <italic>CHRNA2</italic> mutation with BFIS phenotype.</p> </abstract>