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Record W2184580009 · doi:10.1016/j.ajhg.2015.11.005

TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations

2015· article· en· W2184580009 on OpenAlexaff
Jason O'Rawe, Yiyang Wu, Max J. Dörfel, Alan F. Rope, Ping Yee Billie Au, Jillian S. Parboosingh, Sungjin Moon, Maria Kousi, Konstantina Kosma, Christopher Smith, Maria Tzetis, Jane L. Schuette, Robert B. Hufnagel, Carlos E. Prada, Francisco Martı́nez, Carmen Orellana, Jonathan Crain, Alfonso Caro‐Llopis, Silvestre Oltra, Sandra Monfort, Laura T. Jiménez-Barrón, Jeffrey Swensen, Sara Ellingwood, Rosemarie Smith, Han Fang, Sandra Ospina, Nicolette S. den Hollander, David Mittelman, Gareth Highnam, Reid Robison, Edward Yang, Laurence Faivre, Agathe Roubertie, Jean‐Baptiste Rivière, Kristin G. Monaghan, Kai Wang, Erica E. Davis, Nicholas Katsanis, Vera M. Kalscheuer, Edith H. Wang, Kay Metcalfe, Tjitske Kleefstra, A. Micheil Innes, Sophia Kitsiou‐Tzeli, Mónica Rosello, Catherine E. Keegan, Gholson J. Lyon

Bibliographic record

VenueThe American Journal of Human Genetics · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNational Human Genome Research InstituteInstituto de Salud Carlos IIINational Institutes of Health
KeywordsGeneticsPhenotypeTAF1BiologyProbandGeneHypotoniaGene knockdownZebrafishIntellectual disabilitySingle-nucleotide polymorphismMutationGene expressionGenotype

Abstract

fetched live from OpenAlex

We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggested that the phenotype is associated with downregulation of a set of genes notably enriched with genes regulated by E-box proteins. In addition, knockdown and mutant studies of this gene in zebrafish have shown a quantifiable, albeit small, effect on a neuronal phenotype. Our results suggest that mutations in TAF1 play a critical role in the development of this X-linked ID 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 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)0.002
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 score0.006
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0060.001

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 head0.022
GPT teacher head0.254
Teacher spread0.232 · 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

Citations128
Published2015
Admission routes1
Has abstractno

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