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Record W4415658175 · doi:10.1002/ajmg.a.64288

Genome Sequencing Identifies a Heterozygous Deletion of <scp> <i>RBFOX2</i> </scp> in a Family With Congenital Heart Disease: A Case Report

2025· article· en· W4415658175 on OpenAlexafffund
Francesca Jean, Amanda L. Stuart, Julien Marcadier, François P. Bernier, Ryan E. Lamont

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNatural Sciences and Engineering Research Council of CanadaAlberta Children's Hospital Research InstituteGenome Canada
KeywordsExonHeart diseaseGeneGenomeDNA sequencingWhole genome sequencingExome sequencingHuman genome

Abstract

fetched live from OpenAlex

We report a 15-year-old female with hypoplastic left heart syndrome and a strong family history of congenital heart defects. Quad genome sequencing was performed following negative chromosomal microarray and congenital structural heart disease gene panel testing, revealing a heterozygous 144 kb deletion encompassing exons 4-14 of RBFOX2, the entirety of the APOL5 gene, and exon 3 of APOL6 in all affected family members. Although RBFOX2 has been implicated in causing hypoplastic left heart syndrome in animal models, and variants in this gene are enriched in patients with congenital heart disease, this report establishes loss-of-function variants in RBFOX2 as an autosomal dominant cause of hypoplastic left heart syndrome. Furthermore, this case highlights the power of genome sequencing in identifying causative variants in patients who have received nondiagnostic array and panel testing.

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: Case report · Consensus signal: Case report
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.001
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 head0.013
GPT teacher head0.299
Teacher spread0.286 · 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 designCase report
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

Citations0
Published2025
Admission routes2
Has abstractyes

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