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Record W4225880055 · doi:10.1136/jmedgenet-2021-108341

<i>FXR1</i>-related congenital myopathy: expansion of the clinical and genetic spectrum

2022· article· en· W4225880055 on OpenAlexaff
Magdalena Mroczek, Cheryl Longman, Maria Elena Farrugia, S. Kapetanovic García, Didem Ardıçlı, Haluk Topaloğlu, Aurelio Hernández‐Laín, Dıclehan Orhan, Mehmet Alikaşifoğlu, Jennifer Duff, Sabine Specht, Kristen L. Nowak, Gianina Ravenscroft, Katherine R. Chao, Zaheer M. Valivullah, Sandra Donkervoort, Dimah Saade, C. Bönnemann, Volker Straub, Grace Yoon

Bibliographic record

VenueJournal of Medical Genetics · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteMuscular Dystrophy UKNational Health and Medical Research CouncilNational Institutes of HealthNational Eye InstituteGenzymeKurt+Peter FoundationNational Institute of Neurological Disorders and StrokeNational Institute for Health and Care ResearchLimb Girdle Muscular Dystrophy 2i Research FundUltragenyx Pharmaceutical
KeywordsMyopathyCongenital myopathyMuscle biopsyHypotoniaPhenotypeExome sequencingMedicineMuscle weaknessPathologyBiologyBiopsyGeneticsInternal medicineGene

Abstract

fetched live from OpenAlex

Background Biallelic pathogenic variants in FXR1 have recently been associated with two congenital myopathy phenotypes: a severe form associated with hypotonia, long bone fractures, respiratory insufficiency and infantile death, and a milder form characterised by proximal muscle weakness with survival into adulthood. Objective We report eight patients from four unrelated families with biallelic pathogenic variants in exon 15 of FXR1 . Methods Whole exome sequencing was used to detect variants in FXR1 . Results Common clinical features were noted for all patients, which included proximal myopathy, normal serum creatine kinase levels and diffuse muscle atrophy with relative preservation of the quadriceps femoris muscle on muscle imaging. Additionally, some patients with FXR1 -related myopathy had respiratory involvement and required bilevel positive airway pressure support. Muscle biopsy showed multi-minicores and type I fibre predominance with internalised nuclei. Conclusion FXR1 -related congenital myopathy is an emerging entity that is clinically recognisable. Phenotypic variability associated with variants in FXR1 can result from differences in variant location and type and is also observed between patients homozygous for the same variant, rendering specific genotype–phenotype correlations difficult. Our work broadens the phenotypic spectrum of FXR1 -related congenital myopathy.

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)0.001
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.220
Threshold uncertainty score0.276

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 science0.0000.001
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 head0.010
GPT teacher head0.269
Teacher spread0.259 · 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".

Quick stats

Citations4
Published2022
Admission routes1
Has abstractyes

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