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Record W3131082368 · doi:10.1038/s41380-021-01035-y

RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes

2021· article· en· W3131082368 on OpenAlexafffund
Catherine A. Brownstein, Richard S. Smith, Lance H. Rodan, Mark Gorman, Margaret A. Hojlo, Emily A. Garvey, Jianqiao Li, Kristin Cabral, Joshua J. Bowen, Abhijit S. Rao, Casie A. Genetti, Devon Carroll, Emma Deaso, Pankaj B. Agrawal, Jill A. Rosenfeld, Weimin Bi, Jennifer Howe, Dimitri J. Stavropoulos, Adam Hansen, Hesham M. Hamoda, Ferne Pinard, Annmarie Caracansi, Christopher A. Walsh, Eugene J. D’Angelo, Alan H. Beggs, Mehdi Zarrei, Richard A. Gibbs, Stephen W. Scherer, David C. Glahn, Joseph Gonzalez–Heydrich

Bibliographic record

VenueMolecular Psychiatry · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeCanadian Institutes of Health ResearchStanley Center for Psychiatric Research, Broad InstituteNational Institutes of HealthHospital for Sick ChildrenGlaxoSmithKlineUniversity of TorontoBroad InstituteIntellectual and Developmental Disabilities Research CenterBoston Children's Hospital
KeywordsPhenotypeCopy-number variationGeneticsRange (aeronautics)BiologyComputational biologyGeneGenome

Abstract

fetched live from OpenAlex

Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3'-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.

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)0.002
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 score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.001

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 head0.004
GPT teacher head0.203
Teacher spread0.198 · 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

Citations16
Published2021
Admission routes2
Has abstractyes

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