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Record W4280646605 · doi:10.14785/lymphosign-2022-0004

CTLA4 haploinsufficiency caused by a novel heterozygous splice site mutation

2022· article· en· W4280646605 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
venuePublished in a venue whose home country is Canada.

Bibliographic record

VenueLymphoSign Journal · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsHaploinsufficiencyImmune dysregulationAutoimmunityImmunologyExome sequencingCompound heterozygosityAutoimmune lymphoproliferative syndromeImmune systemProbandCommon variable immunodeficiencyMedicineMutationBiologyGeneticsPhenotypeAntibodyGeneFas receptor

Abstract

fetched live from OpenAlex

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) haploinsufficiency is characterized by a variety of phenotypes, ranging from autoimmune disorders, enteropathy, fatal combined immunodeficiency, as well as lymphoproliferation and malignancy. Aim: To broaden the genotypic spectrum and clinical presentations of patients with CTLA4 variants. Methods: We evaluated a female patient with autoimmunity and lymphopenia. Immune workup and whole exome sequencing (WES) were performed. Results: The proband presented at 11 years of age with hypothyroidism and later developed Evans syndrome, alopecia, eczema, and lymphocytic interstitial pneumonia. Immune evaluation revealed T, B, and NK lymphopenia with normal humoral immunity. Following a negative genetic panel for autoimmune lymphoproliferative syndrome (ALPS), WES analysis identified a novel heterozygous intronic variant predicted in-silico to cause skipping of exon 2 of the CTLA4 gene. Conclusion: A novel heterozygous mutation in CTLA4 caused variable presentations of immune dysregulation, one of the hallmarks of CTLA4 haploinsufficiency. Statement of Novelty: We herein report a novel mutation in CTLA4 resulting in various features of autoimmunity.

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.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies, Insufficient payload (model declined to judge)
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 score0.899
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0020.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.008
GPT teacher head0.207
Teacher spread0.199 · 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