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Record W2559857749 · doi:10.1212/nxg.0000000000000115

FHF1 (FGF12) epileptic encephalopathy

2016· article· en· W2559857749 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.
aboutThe title or abstract carries a Canadian signal from the geographic lexicon.

Bibliographic record

VenueNeurology Genetics · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsUniversité de MontréalHôpital Notre-DameCentre Hospitalier Universitaire Sainte-Justine
FundersUniversity of TorontoGenome CanadaNational Institute for Health and Care ResearchNational Institute of Neurological Disorders and StrokeOntario Brain InstituteWellcome TrustMcGill University
KeywordsMedicineEpilepsySanger sequencingMutationBioinformaticsPsychiatryGeneticsGeneBiology

Abstract

fetched live from OpenAlex

Voltage-gated sodium channels (Navs) are mainstays of neuronal function, and mutations in the genes encoding CNS Navs (Nav1.1 [ SCN1A ], Nav1.2 [ SCN2A ], Nav1.3 [ SCN3A ], and Nav1.6 [ SCN8A ]) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE).1 Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the C-terminal tails of Navs to modulate the channels' fast, and long-term, inactivations.2 FHF2 mutation is a rare cause of generalized epilepsy with febrile seizures plus (GEFS+).3 Recently, a de novo FHF1 mutation (p.R52H) was reported in early-onset EE in 2 siblings.4 We report 3 patients from unrelated families with the same FHF1 p.R52H mutation. The 5 cases together frame the FHF1 R52H EE from infancy to adulthood. As discussed below, this gain-of-function disease may be amenable to personalized therapy. Acknowledgment: The study has UK Research Ethics Committee's approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research through the Comprehensive Clinical Research Network, the Health Innovation Challenge Fund (grant HICF-1009-003), and the Wellcome Trust Sanger Institute (grant WT098051). BAM holds the University of Toronto Michael Bahen Chair in Epilepsy Research. The authors thank the Next Generation Sequencing/bioinformatics teams at McGill University, the Genome Quebec Innovation Center, the Réseau de Médecine Génétique Appliquée, and Drs. Ledia Brunga (DNA sample management); Dipayan Mitra (MRI); Ms. Gail Charlton (EEG); and Ms. Sylvia Dobrzeniecka (sequencing) for their efforts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.656
Threshold uncertainty score0.750

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.214
Teacher spread0.207 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it