Evidence map›Paper›PMID 41642117›Full record

ArticleEpilepsia2026

Mechanisms of SCN2A loss of function do not predict presence or phenotype of epilepsy.

Marsha Tan, Beatrice Southby Goad, Meagan Allen, Jill Rodda, Kay L Richards, Simone L Ardern-Holmes, Daniel Bamborschke, Daniel Fritzen, Inna Hughes, Kate Riney and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026
    Review
  2. Article
  3. 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

24 authors.

Marsha TanIon Channels and Human Disease Group, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-0648-0813
Beatrice Southby GoadMurdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0003-3210-0447
Meagan AllenMurdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID https://orcid.org/0009-0004-4917-9395
Jill RoddaMurdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0003-4486-8111
Kay L RichardsIon Channels and Human Disease Group, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-5707-9448
Simone L Ardern-HolmesT. Y. Nelson Department of Neurology and Neurosurgery, Children's Hospital at Westmead, Sydney, New South Wales, Australia.ORCID https://orcid.org/0000-0002-9031-7348
Daniel BamborschkeDepartment of Pediatric Neurology, Children's Hospital, University Hospital, Bonn, Germany.ORCID https://orcid.org/0000-0002-9868-0184
Daniel FritzenDepartment of Pediatric Neurology, Children's Hospital, University Hospital, Bonn, Germany.ORCID https://orcid.org/0009-0000-1678-0441
Inna HughesDepartment of Neurology, University of Rochester Medical Center, Rochester, New York, USA.ORCID https://orcid.org/0000-0003-3585-3567
Kate RineyNeurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-1122-3555
Ana Roche MartinezParc Taulí Hospital Universitari, Institut d'Investigació i Innovació, Barcelona, Spain.ORCID https://orcid.org/0000-0001-8295-1982
Angelo RussoIstituto di Ricovero e Cura a Carattere Scientifico Istituto Delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria Dell'età Pediatrica, Bologna, Italy.ORCID https://orcid.org/0000-0002-0322-2640
Adriane SinclairNeurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-2341-3065
Stefano SartoriPediatric Neurology and Neurophysiology Unit, University Hospital of Padua, Padua, Italy.ORCID https://orcid.org/0000-0002-0012-6848
Marina TrivisanoNeurology, Epilepsy, and Movement Disorders Unit, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, full member of European Reference Network EpiCARE, Rome, Italy.ORCID https://orcid.org/0000-0002-9841-8581
Angela De DominicisNeurology, Epilepsy, and Movement Disorders Unit, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, full member of European Reference Network EpiCARE, Rome, Italy.ORCID https://orcid.org/0000-0002-8526-1511
Nicola SpecchioNeurology, Epilepsy, and Movement Disorders Unit, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, full member of European Reference Network EpiCARE, Rome, Italy.ORCID https://orcid.org/0000-0002-8120-0287
Rikke S MøllerDepartment of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, member of European Reference Network EpiCARE, Dianalund, Denmark.ORCID https://orcid.org/0000-0002-9664-1448
Ingrid E SchefferMurdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-2311-2174
Walid FazeliDepartment of Pediatric Neurology, Children's Hospital, University Hospital, Bonn, Germany.ORCID https://orcid.org/0000-0002-9425-5535
Markus WolffSwiss Epilepsy Center, Klinik Lengg, Zürich, Switzerland.ORCID https://orcid.org/0000-0001-5640-0888
Steven PetrouIon Channels and Human Disease Group, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-4960-6375
Katherine B HowellMurdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-5469-8411
Géza BereckiIon Channels and Human Disease Group, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.ORCID https://orcid.org/0000-0002-8664-6325

Funding

Medical Research Future Fund (MRFF) GHFMCDI000002Murdoch Children's Research Institute (MCRI)Praxis Precision Medicines, Inc.RogConVictorian State Government Operational Infrastructure Support Program
6 · The paper itself

Abstract

objectiveSCN2A loss-of-function (LoF) variants are associated with epilepsy (onset age ≥ 3 months), intellectual disability (ID), and autism spectrum disorder (ASD). Despite numerous identified variants and the description of phenotypic subgroups, relationships between Na

methodsWhole-cell patch-clamp electrophysiology was used to characterize 15 presumed LoF SCN2A variants. Mechanism-phenotype correlations were assessed in 33 patients with these variants (six recurrent) and 41 patients with 15 previously characterized LoF variants (four recurrent). Phenotypic subgroups were categorized as later onset epilepsy-midinfancy (onset between 3 and 18 months), later onset epilepsy-childhood (onset after 18 months), ID/ASD without epilepsy, and "other" for unclassified cases.

resultsOf the 15 electrophysiologically characterized SCN2A variants, 11 caused total Na SIGNIFICANCE: Distinct SCN2A LoF phenotypes cannot be reliably linked to specific biophysical mechanisms, as both total and partial Na

Indexed as

EpilepsyLoss of Function MutationNAV1.2 Voltage-Gated Sodium ChannelAdolescentAdultAutism Spectrum DisorderChildChild, PreschoolFemaleHumansInfantIntellectual DisabilityMalePatch-Clamp TechniquesPhenotypeNAV1.2 Voltage-Gated Sodium ChannelSCN2A protein, humanclinical phenotypede novo variantepilepsyloss of functionNav1.2 channelpatch‐clampSCN2A

Identifiers

PMID41642117
PMCPMC13179650

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.