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Record W4206099619 · doi:10.1002/humu.24332

Delineation of a novel neurodevelopmental syndrome associated with <i>PAX5</i> haploinsufficiency

2022· article· en· W4206099619 on OpenAlexaff
Yoel Gofin, Tianyun Wang, Madelyn A. Gillentine, Tiana M. Scott, Aliska M. Berry, Mahshid S. Azamian, Casie A. Genetti, Pankaj B. Agrawal, Jonathan Picker, Monica H. Wojcik, Mauricio R. Delgado, Sally Ann Lynch, Stephen W. Scherer, Jennifer Howe, Carlos A. Bacino, Stephanie DiTroia, Grace E. VanNoy, Anne O’Donnell‐Luria, Seema R. Lalani, W. Graf, Jill A. Rosenfeld, Evan E. Eichler, Rachel K. Earl, Daryl A. Scott

Bibliographic record

VenueHuman Mutation · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersNational Institutes of HealthNational Human Genome Research InstituteNational Institute of Mental HealthEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentSimons Foundation Autism Research InitiativeSilicon Valley Community Foundation
KeywordsMedical schoolHaploinsufficiencyMedicineGerontologyGeneticsBiologyMedical educationGene

Abstract

fetched live from OpenAlex

PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues. Four of these individuals were published previously but without detailed clinical descriptions. All these individuals have been diagnosed with one or more neurodevelopmental phenotypes including delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. Seizures were documented in four individuals. No recurrent patterns of brain magnetic resonance imaging (MRI) findings, structural birth defects, or dysmorphic features were observed. Our findings suggest that PAX5 haploinsufficiency causes a neurodevelopmental disorder whose cardinal features include DD, variable ID, and/or ASD.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.941
Threshold uncertainty score0.415

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 head0.014
GPT teacher head0.230
Teacher spread0.215 · 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 designBench or experimental
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
Published2022
Admission routes1
Has abstractyes

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