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Record W4311448329 · doi:10.1056/nejmoa2207406

Deep Intronic <i>FGF14</i> GAA Repeat Expansion in Late-Onset Cerebellar Ataxia

2022· article· en· W4311448329 on OpenAlexafffundabout
David Pellerin, Matt C. Danzi, Carlo Wilke, M. Renaud, Sarah Fazal, Marie‐Josée Dicaire, Carolin K. Scriba, Catherine Ashton, Christopher Yanick, Danique Beijer, Adriana Rebelo, Clarissa Rocca, Zane Jaunmuktane, Joshua A. Sonnen, Roxanne Larivière, David Genı́s, Laura Molina‐Porcel, Karine Choquet, Rawan Sakalla, Sylvie Provost, Rebecca Robertson, Xavier Allard‐Chamard, Martine Tétreault, Sarah J. Reiling, Sara Nagy, Vikas Nishadham, Meera Purushottam, Seena Vengalil, Mainak Bardhan, Atchayaram Nalini, Zhongbo Chen, Jean Mathieu, Rami Massie, Colin Chalk, Anne‐Louise Lafontaine, François Evoy, Marie‐France Rioux, Jiannis Ragoussis, Kym M. Boycott, Marie‐Pierre Dubé, Antoine Duquette, Henry Houlden, Gianina Ravenscroft, Nigel G. Laing, Phillipa J. Lamont, Mario Saporta, Rebecca Schüle, Lüdger Schöls, Roberta La Piana, Matthis Synofzik, Stephan Züchner, Bernard Brais

Bibliographic record

VenueNew England Journal of Medicine · 2022
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsUniversity of OttawaUniversité de SherbrookeMcGill Genome CentreUniversité de MontréalChildren's Hospital of Eastern OntarioCentre Hospitalier de l’Université de MontréalMcGill UniversityMontreal Neurological Institute and HospitalMontreal Heart Institute
FundersFondation Groupe MonacoNational Institute of Neurological Disorders and StrokeNational Health and Medical Research CouncilMedical Research CouncilMedizinischen Fakultät, Eberhard Karls Universität TübingenLeonard M. Miller School of MedicineNational Institutes of HealthFondation de l'Hôpital Général de MontréalUniversitat de BarcelonaElse Kröner-Fresenius-StiftungUniversity College London Hospitals NHS Foundation TrustEberhard Karls Universität TübingenInstitut National de la Santé et de la Recherche MédicaleEuropean CommissionNational Institute of Mental Health and NeurosciencesWellcome TrustUniversity College LondonCanadian Institutes of Health ResearchRoyal College of Physicians and Surgeons of CanadaMcGill UniversityDeutsche ForschungsgemeinschaftGenome CanadaBrain Research UKBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchChildren's Hospital of Eastern Ontario FoundationOntario GenomicsCanada Foundation for InnovationDeutsches Zentrum für Neurodegenerative ErkrankungenOntario Genomics InstituteGénome QuébecNational Institute of Mental HealthUniversität BaselAustralian GovernmentFondation du Grand défi Pierre LavoieUniversité de LorraineUniversity of Miami
KeywordsTrinucleotide repeat expansionOdds ratioAtaxiaBiologyInternal medicineGeneticsMedicineNeuroscienceGeneAllele

Abstract

fetched live from OpenAlex

BACKGROUND: The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis. METHODS: We sequenced the genomes of six persons with autosomal dominant LOCA who were members of three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between the repeat expansion and disease in two independent case-control series - one French Canadian (66 patients and 209 controls) and the other German (228 patients and 199 controls). We also genotyped the repeat in 20 Australian and 31 Indian index patients. We assayed gene and protein expression in two postmortem cerebellum specimens and two induced pluripotent stem-cell (iPSC)-derived motor-neuron cell lines. RESULTS: RNA and protein. CONCLUSIONS: was found to be associated with LOCA. (Funded by Fondation Groupe Monaco and others.).

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.122
Threshold uncertainty score0.243

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.020
GPT teacher head0.259
Teacher spread0.239 · 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 source (direct Gemma or distilled Codex), 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".

Quick stats

Citations243
Published2022
Admission routes3
Has abstractyes

Explore more

Same venueNew England Journal of MedicineSame topicGenetic Neurodegenerative DiseasesFrench-language works237,207