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Record W3200821844 · doi:10.1002/ajmg.a.62494

A <i>de novo</i><scp><i>CSDE1</i></scp> variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents

2021· article· en· W3200821844 on OpenAlexafffund
Andrea Gangfuß, Hanns Lochmüller, Ana Töpf, Emily O’Heir, Rita Horváth, Heike Kölbel, Bernd Schweiger, Ulrike Schara‐Schmidt, Andreas Roos

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsOttawa HospitalChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersNational Eye InstituteMedical Research CouncilEvelyn TrustHorizon 2020 Framework ProgrammeCanadian Institutes of Health ResearchH2020 European Research CouncilAtaxia UKMuscular Dystrophy CanadaMedical Research Council CanadaNewton FundCanada Foundation for InnovationNational Human Genome Research InstituteWellcome TrustFrench Muscular Dystrophy AssociationEuropean Regional Development FundBroad Institute
KeywordsIntellectual disabilityAutismAutism spectrum disorderNeurodevelopmental disorderGlobal developmental delayCorpus callosumGeneticsPhenotypeGeneMedicineBiologyBioinformaticsNeurosciencePsychiatry

Abstract

fetched live from OpenAlex

CSDE1 encodes the cytoplasmic cold shock domain-containing protein E1 (CSDE1), which is highly conserved across species and functions as an RNA-binding protein involved in translationally coupled mRNA turnover. CSDE1 displays a bidirectional role: promoting and repressing the translation of RNAs but also increasing and decreasing the abundance of RNAs. Preclinical studies highlighted an involvement of CSDE1 in different forms of cancer. Moreover, CSDE1 is highly expressed in human embryonic stem cells and plays a role in neuronal migration and differentiation. A genome-wide association study suggested CSDE1 as a potential autism-spectrum disorder risk gene. A multicenter next generation sequencing approach unraveled likely causative heterozygous variants in CSDE1 in 18 patients, identifying a new autism spectrum disorder-related syndrome consisting of autism, intellectual disability, and neurodevelopmental delay. Since then, no further patients with CSDE1 variants have been reported in the literature. Here, we report a 9.5-year-old girl from a consanguineous family of Turkish origin suffering from profound delayed speech and motor development, moderate intellectual disability, neurologic and psychiatric symptoms as well as hypoplasia of corpus callosum and mildly reduced brain volume on brain magnetic resonance imaging associated with a recurrent de novo mutation in CSDE1 (c.367C > T; p.R123*) expanding the phenotypical spectrum associated with pathogenic CSDE1 variants.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: Case report
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0020.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.270
Teacher spread0.261 · 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 designCase report
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

Citations6
Published2021
Admission routes2
Has abstractyes

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Same venueAmerican Journal of Medical Genetics Part ASame topicRNA Research and SplicingFrench-language works237,207