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Record W4308447892 · doi:10.1002/ggn2.202200012

Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age

2022· article· en· W4308447892 on OpenAlexaff
Catherine A. Brownstein, Élise Douard, Robin L. Haynes, Hyun Yong Koh, Alireza Haghighi, Christine Keywan, Bree Martin, Sanda Alexandrescu, Elisabeth A. Haas, Sara O. Vargas, Monica H. Wojcik, Sébastien Jacquemont, Annapurna Poduri, Richard D. Goldstein, Ingrid A. Holm

Bibliographic record

VenueAdvanced Genetics · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Mental HealthBoston Children's HospitalNational Heart, Lung, and Blood InstituteNational Institutes of HealthNational Institute of Child Health and Human Development
KeywordsCopy-number variationCohortAutismIntellectual disabilitySchizophrenia (object-oriented programming)MedicineMedical geneticsGeneticsCohort studyAutism spectrum disorderBiologyPediatricsPsychiatryInternal medicineGenomeGene

Abstract

fetched live from OpenAlex

Abstract In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well‐studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months. CNVs are classified using the American College of Medical Genetics and Genomics guidelines and CNVs in our cohort are compared to an autism spectrum disorder (ASD) cohort, and to a control cohort. Pathogenic CNVs are identified in 5 of 116 cases (4.3%). Variants of uncertain significance (VUS) favoring pathogenic CNVs are identified in 9 cases (7.8%). Several CNVs are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, and schizophrenia. The structural variant 47,XXY is identified in two cases (2/69 boys, 2.9%) not previously diagnosed with Klinefelter syndrome. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls ( p = 0.007) and are not significantly different from the ASD cohort. The finding of pathogenic or VUS favoring pathogenic CNVs, or structural variants, in 12.1% of cases, combined with the observation of higher pathogenicity scores for deletions in SUDP versus controls, suggests that CMA should be included in the genetic evaluation of SUDP.

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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.175
Threshold uncertainty score0.423

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 head0.009
GPT teacher head0.243
Teacher spread0.234 · 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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