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Record W4392086794 · doi:10.1111/cge.14498

Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global <scp>DNA</scp> methylation profile

2024· article· en· W4392086794 on OpenAlexafffund
Dmitrijs Rots, Kathleen Rooney, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Rolph Pfundt, Carlo Marcelis, Marjolein H. Willemsen, Johanna M. van Hagen, Petra Zwijnenburg, Mariëlle Alders, Katrin Õunap, Tiia Reimand, Olga Fjodorova, Siren Berland, Eva Benedicte Liahjell, Ognjen Bojović, Marjolein Kriek, Claudia Ruivenkamp, Maria Teresa Bonati, Han G. Brunner, Lisenka E.L.M. Vissers, Bekim Sadiković, Tjitske Kleefstra

Bibliographic record

VenueClinical Genetics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsLondon Health Sciences CentreWestern University
FundersNederlandse Organisatie voor Wetenschappelijk OnderzoekEuropean CommissionEesti TeadusagentuurGovernment of CanadaGenome CanadaOntario GenomicsOntario Genomics Institute
KeywordsGene duplicationDNA methylationGeneticsLocus (genetics)Neurodevelopmental disorderGeneBiologyAutismAutism spectrum disorderMedicineGene expressionPsychiatry

Abstract

fetched live from OpenAlex

Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non-syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.628
Threshold uncertainty score0.916

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 head0.025
GPT teacher head0.306
Teacher spread0.281 · 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

Citations7
Published2024
Admission routes2
Has abstractyes

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