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Record W4414146401 · doi:10.1002/ajmg.a.64242

De Novo Truncating Variants in <scp> <i>ZNF865</i> </scp> Cause a Novel Neurodevelopmental Disorder

2025· article· en· W4414146401 on OpenAlexaff
Samuel M Bradbrook, Gail E. Graham, Melissa T. Carter, Maria Kibæk, Christina Fagerberg, Martin J. Larsen, Katherine Dawson, Cheryl Meuter, Alexander Pepler, Thomas Besnard, Marie Vincent, Bertrand Isidor, Stéphane Bezieau, Benjamin Cogné, Kathrine Bjørgo, Silja Svanstrøm Amundsen, Thomas Courtin, Lisa Emrick, Jill A. Rosenfeld, Monika Weisz‐Hubshman, Bryan C. Mak, Julián A. Martínez-Agosto, Mathilde Heulin, Gilles Morin, Boris Keren, Sacha Schutz, Pauline Monin, Mathilde Pujalte, Louis Januel, Gaëtan Lesca, Marie‐Noëlle Bonnet‐Dupeyron Valence, Henri Margot, Jonathan Lévy, Emmanuela Iovino, Federica Isidori, Tommaso Pippucci, Francesca Montanari, Lauren Bell, Jennifer Burton, Erin Torti, Ingrid M. Wentzensen, Julien Marcadier

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsChildren's Hospital of Eastern OntarioAlberta Children's Hospital
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentIntellectual and Developmental Disabilities Research CenterNational Institutes of Health
KeywordsExome sequencingZinc fingerGeneExomePhenotypeGenomeDNA sequencingHuman genomeNeurodevelopmental disorder

Abstract

fetched live from OpenAlex

Despite significant knowledge advances in recent decades, the role of most protein-coding genes in human disease remains incompletely understood. Exome sequencing continues to improve our understanding by elucidating novel genotype-phenotype associations. Across multiple healthcare centers, either exome or genome sequencing was performed in 18 patients with shared features of global developmental delay, hypotonia, and dysmorphisms. De novo, truncating variants in ZNF865 were identified in all 18 patients, with all but one clustered toward the C-terminus. Four variants were seen more than once in unrelated patients. No disease-causing variants were identified in other genes that would explain the patients' phenotypes. Little is known of the function of ZNF865, which belongs to the poly-zinc finger family of proteins that contain a large array of tandem C2H2 zinc finger DNA binding domains. Our findings suggest that protein-truncating variants in this gene lead to intellectual disability with a recognizable phenotypic pattern.

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)0.000
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 score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.007
GPT teacher head0.265
Teacher spread0.258 · 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

Citations1
Published2025
Admission routes1
Has abstractyes

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Same venueAmerican Journal of Medical Genetics Part ASame topicGenomics and Rare DiseasesFrench-language works237,207