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Record W3082500506 · doi:10.1002/mdc3.13086

Channelopathies Are a Frequent Cause of Genetic Ataxias Associated with Cerebellar Atrophy

2020· article· en· W3082500506 on OpenAlex
Laurence Gauquelin, Taila Hartley, Mark A. Tarnopolsky, David A. Dyment, Bernard Brais, Michael T. Geraghty, Martine Tétreault, Sohnee Ahmed, Samantha K. Rojas, Karine Choquet, Jacek Majewski, François P. Bernier, A. Micheil Innes, Guy A. Rouleau, Oksana Suchowersky, Kym M. Boycott, Grace Yoon

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

VenueMovement Disorders Clinical Practice · 2020
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsUniversity of AlbertaHospital for Sick ChildrenUniversité de MontréalMontreal Neurological Institute and HospitalMcGill Genome CentreUniversity of CalgaryUniversity of OttawaMcGill UniversityChildren's Hospital of Eastern OntarioUniversity of TorontoSickKids FoundationMcMaster University Medical Centre
FundersGenome AlbertaGenome British ColumbiaGénome QuébecCanadian Institutes of Health ResearchGenome CanadaOntario GenomicsOntario Genomics Institute
KeywordsExome sequencingAtrophyMedicineGenetic testingSpinocerebellar ataxiaCerebellar ataxiaAtaxiaCohortPathologyDiseaseGeneticsInternal medicineBiologyMutationPsychiatryGene

Abstract

fetched live from OpenAlex

BACKGROUND: Cerebellar atrophy is a nonspecific imaging finding observed in a number of neurological disorders. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of conditions, rendering the approach to diagnosis challenging. OBJECTIVES: To define the spectrum of genetic ataxias associated with cerebellar atrophy in a Canadian cohort and the diagnostic yield of exome sequencing for this group of conditions. METHODS: A total of 92 participants from 66 families with cerebellar atrophy were recruited for this multicenter prospective cohort study. Exome sequencing was performed for all participants between 2011 and 2017 as part of 1 of 2 national research programs, Finding of Rare Genetic Disease Genes or Enhanced Care for Rare Genetic Diseases in Canada. RESULTS: A genetic diagnosis was established in 53% of families (35/66). Pathogenic variants were found in 21 known genes, providing a diagnosis for 31/35 families (89%), and in 4 novel genes, accounting for 4/35 families (11%). Of the families, 31/66 (47%) remained without a genetic diagnosis. The most common diagnoses were channelopathies, which were established in 9/35 families (26%). Additional clinical findings provided useful clues to specific diagnoses. CONCLUSIONS: We report on the high frequency of channelopathies as a cause of genetic ataxias associated with cerebellar atrophy and the utility of exome sequencing for this group of conditions.

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)0.026
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.163
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.026
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.080
GPT teacher head0.328
Teacher spread0.249 · 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