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Record W2976674170 · doi:10.1038/s41431-019-0519-x

Severe neurodevelopmental disease caused by a homozygous TLK2 variant

2019· article· en· W2976674170 on OpenAlexaff
Ana Töpf, Yavuz Oktay, B. Sunitha, Elmasnur Yilmaz, Ece Sönmezler, Uluç Yiş, Steven Laurie, Rachel Thompson, Andreas Roos, Daniel G. MacArthur, Ahmet Yaramış, Serdal Güngör, Hanns Lochmüller, Semra Hız, Rita Horváth

Bibliographic record

VenueEuropean Journal of Human Genetics · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsOttawa HospitalChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteTürkiye Bilimsel ve Teknolojik Araştırma KurumuMedical Research CouncilNewton FundBroad InstituteNational Eye InstituteWellcome Trust
KeywordsMissense mutationHaploinsufficiencyGeneticsExome sequencingBiologyPhenotypeExonCompound heterozygosityDiseaseExomeGeneNeurodevelopmental disorderHeterozygote advantageAlleleMedicinePathology

Abstract

fetched live from OpenAlex

A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism.

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 score0.892
Threshold uncertainty score0.678

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 head0.007
GPT teacher head0.207
Teacher spread0.201 · 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

Citations15
Published2019
Admission routes1
Has abstractyes

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