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Record W2899047922 · doi:10.1002/mgg3.492

Triple A syndrome presenting as complicated hereditary spastic paraplegia

2018· article· en· W2899047922 on OpenAlexafffund
Etienne Léveillé, Hernán Gonorazky, Marie‐France Rioux, Lili‐Naz Hazrati, Jennifer A. Ruskey, Amanda Carnevale, Dan Spiegelman, Alexandre Dionne‐Laporte, Guy A. Rouleau, Grace Yoon, Ziv Gan‐Or

Bibliographic record

VenueMolecular Genetics & Genomic Medicine · 2018
Typearticle
Languageen
FieldNeuroscience
TopicHereditary Neurological Disorders
Canadian institutionsUniversité de SherbrookeMontreal Neurological Institute and HospitalUniversity of TorontoSickKids FoundationHospital for Sick ChildrenMcGill University
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health Research
KeywordsMedicineHereditary spastic paraplegiaExome sequencingSpasticityPediatricsNonsense mutationParaplegiaAchalasiaSpasticMutationPathologyBioinformaticsInternal medicineMissense mutationGeneticsPhysical therapySpinal cord

Abstract

fetched live from OpenAlex

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of rare disorders characterized by spastic paraparesis and other symptoms. Often, other diseases can mimic HSP, which may delay diagnosis and treatment. METHODS: Whole exome sequencing was performed in families with clinically suspected HSP without a genetic diagnosis. RESULTS: We report three patients from two families who presented with lower limb spasticity, muscular atrophy, and other neurological symptoms, who were clinically diagnosed with complicated HSP. Whole exome sequencing revealed bi-allelic AAAS nonsense mutations; one individual was homozygous for the p.(Arg478*) mutation, and two siblings were homozygous for the p.(Arg286*) mutation, leading to the diagnosis of triple A syndrome. This rare syndrome is typically characterized by a triad of symptoms: achalasia, adrenal insufficiency, and alacrima, and is often accompanied by other neurological abnormalities. CONCLUSIONS: Our findings suggest that triple A syndrome should be suspected in complicated HSP patients without a known genetic cause, especially if at least one of the main triad of triple A syndrome symptoms is present.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.441
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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 head0.036
GPT teacher head0.283
Teacher spread0.247 · 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; both teacher heads agree on what is shown here.

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

Citations11
Published2018
Admission routes2
Has abstractyes

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