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Two Definite Sudden Unexpected Deaths in Epilepsy in a Family with a DEPDC5 Mutation (P6.365)

2016· article· en· W2521328099 on OpenAlexaffabout
Fabio Nascimento e Silva, Felippe Borlot, Patrick Cossette, Berge A. Minassian, Danielle M. Andrade

Bibliographic record

VenueNeurology · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicATP Synthase and ATPases Research
Canadian institutionsUniversity of TorontoHospital for Sick ChildrenCentre Hospitalier de l’Université de Montréal
Fundersnot available
KeywordsEpilepsyMutationMedicinePediatricsPsychiatryGeneticsBiology

Abstract

fetched live from OpenAlex

OBJECTIVE and BACKGROUND: DEPDC5 gene, mapped to 22q12.2-q12.3, has been associated with a variety of familial epilepsies. Notably, DEPDC5 has never been linked to increased risk of sudden unexpected death in epilepsy (SUDEP). METHODS: Case report. RESULTS: We studied a three-generation, non-consanguineous, French-Canadian family with nine clinically affected individuals. Interestingly, all but one are males. The index case is a 39-year-old man who started having seizures at the age of 13 years. His seizures were characterized by a “dream-like” aura followed by loss of consciousness and tonic-clonic movements. Initially, seizures were mainly diurnal. In his mid-20s, the episodes became exclusively nocturnal. EEGs showed interictal epileptiform discharges over the right anterior-temporal region. Brain MRI was unremarkable. Two of the index case's paternal uncles suffered definite autopsy-confirmed SUDEP, at the ages of 58 and 50 years, respectively. Seizure-history in this family can be summarized by an onset before reaching adulthood, followed by subsequent progressive decrease in seizure frequency. Seizures were predominantly nocturnal secondarily generalized tonic-clonic. All the subjects were cognitively intact. There was no history of any cardiac symptomatology, cardiovascular risk factor, or definite cardiac condition. Genetic analysis of the index case revealed a pathogenic heterozygous variant in the DEDPC5 gene (p.Gln216, c.646C>T; ENST00000536766). The index case was also tested for genes associated with SUDEP, none of which showed mutations. All living affected relatives, as well as four healthy family members, were clinically evaluated and had DEPDC5 Sanger sequenced. All affected subjects and one healthy individual were found to carry the same DEPDC5 pathogenic variant as the index case. CONCLUSIONS: Several genes have been linked with SUDEP. These are associated with cardiac arrhythmias and/or severe epilepsies, both of which do not apply to this family’s phenotype. The finding in this family suggests that DEPDC5 mutations may be a risk factor for SUDEP.

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.

How this classification was reachedexpand

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.672
Threshold uncertainty score0.410

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 head0.013
GPT teacher head0.273
Teacher spread0.260 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2016
Admission routes2
Has abstractyes

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