Evidence map›Paper›PMID 25770198›Full record

ArticleNeurology2015

Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.

Valerio Conti, Patrizia Aracri, Laura Chiti, Simone Brusco, Francesco Mari, Carla Marini, Maria Albanese, Angela Marchi, Claudio Liguori, Fabio Placidi and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Towards Zebrafish Models of CNS Channelopathies.International journal of molecular sciences · 2022
    Review
  7. Review
  8. Nicotinic Acetylcholine Receptors of PC12 Cells.Cellular and molecular neurobiology · 2021
    Review
  9. Paroxysmal Movement Disorders.Frontiers in neurology · 2021
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Frontiers in molecular neuroscience · 2019
    Article
  15. Review
  16. Review
  17. Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Valerio ContiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Patrizia AracriFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Laura ChitiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Simone BruscoFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Francesco MariFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Carla MariniFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Maria AlbaneseFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Angela MarchiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Claudio LiguoriFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Fabio PlacidiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Andrea RomigiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Andrea BecchettiFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy.
Renzo GuerriniFrom the Pediatric Neurology and Neurogenetics Unit and Laboratories (V.C., L.C., F.M., C.M., R.G.), A. Meyer Children's Hospital-University of Florence; Department of Biotechnology and Biosciences and Center of Neuroscience (P.A., S.B., A.B.), Università di Milano-Bicocca, Milan; Neurophysiopathology Unit (M.A., A.M., C.L., F.P., A.R.), Sleep and Epilepsy Center, Department of Systems Medicine, University of Rome Tor Vergata General Hospital, Rome; IRCCS Neuromed (A.R.), Pozzilli, Isernia; and IRCCS Stella Maris Foundation (R.G.), Calambrone, Pisa, Italy. r.guerrini@meyer.it.
Meyer Children's Hospital · IT

Funding

Telethon GGP12147
6 · The paper itself

Abstract

objectiveWe assessed the mutation frequency in nicotinic acetylcholine receptor (nAChR) subunits CHRNA4, CHRNB2, and CHRNA2 in a cohort including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and sporadic nocturnal frontal lobe epilepsy (NFLE). Upon finding a novel mutation in CHRNA2 in a large family, we tested in vitro its functional effects.

methodsWe sequenced all the coding exons and their flanking intronic regions in 150 probands (73 NFLE, 77 ADNFLE), in most of whom diagnosis had been validated by EEG recording of seizures. Upon finding a missense mutation in CHRNA2, we measured whole-cell currents in human embryonic kidney cells in both wild-type and mutant α2β4 and α2β2 nAChR subtypes stimulated with nicotine.

resultsWe found a c.889A>T (p.Ile297Phe) mutation in the proband (≈0.6% of the whole cohort) of a large ADNFLE family (1.2% of familial cases) and confirmed its segregation in all 6 living affected individuals. Video-EEG studies demonstrated sleep-related paroxysmal epileptic arousals in all mutation carriers. Oxcarbazepine treatment was effective in all. Whole-cell current density was reduced to about 40% in heterozygosity and to 0% in homozygosity, with minor effects on channel permeability and sensitivity to nicotine.

conclusionADNFLE had previously been associated with CHRNA2 dysfunction in one family, in which a gain of function mutation was demonstrated. We confirm the causative role of CHRNA2 mutations in ADNFLE and demonstrate that also loss of function of α2 nAChRs may have pathogenic effects. CHRNA2 mutations are a rare cause of ADNFLE but this gene should be included in mutation screening.

Indexed as

AdolescentAdultChildChild, PreschoolCohort StudiesEpilepsy, Frontal LobeFemaleGenotypeHumansMaleMiddle AgedParasomniasPedigreeReceptors, NicotinicCHRNA2 protein, humanReceptors, Nicotinic

Identifiers

PMID25770198
PMCPMC4408286
OpenAlexW2070591715

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