title: Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.
abstract: 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 CHRNA2 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 CHRNA2 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 CHRNA2-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 CHRNA2 mutation with BFIS phenotype.
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Trivisano
authors.affiliation: Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
authors.affiliation: Department of Biochemical Science "Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Milano
authors.affiliation: Unit of Clinical Psychology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cappelletti
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.|Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pietrafusa
authors.affiliation: Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Enrico Silvio
authors.initials: ES
authors.lastname: Bertini
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Vigevano
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Specchio
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D020936:Epilepsy, Benign Neonatal / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: C436489:CHRNA2 protein, human; D011978:Receptors, Nicotinic; D001120:Arginine
keywords: Acetylcholine receptor; Autosomal dominant nocturnal frontal lobe epilepsy; Benign epilepsies; Benign familial infantile epilepsies; CHRNA2 gene