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The E326K mutation and Gaucher disease: mutation or polymorphism?

2002· article· en· W1572882831 on OpenAlex
Joseph K. Park, Nahid Tayebi, BK Stubblefield, ME LaMarca, Jennifer MacKenzie, D Stone, Ellen Sidransky

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.

Bibliographic record

VenueClinical Genetics · 2002
Typearticle
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsQueen's University
Fundersnot available
KeywordsGlucocerebrosidaseAlleleMutationGeneticsBiologyPoint mutationPopulationGaucher's diseaseGeneDiseaseMedicineInternal medicine

Abstract

fetched live from OpenAlex

Gaucher disease is caused by mutations in the gene for human glucocerebrosidase, a lysosomal enzyme involved in the intracellular hydrolysis of glucosylceramide. While over 150 different glucocerebrosidase mutations have been identified in patients with Gaucher disease, not all reported mutations have been fully characterized as being causative. One such mutation is the E326K mutation, which results from a G to A nucleotide substitution at genomic position 6195 and has been identified in patients with type 1, type 2 and type 3 Gaucher disease. However, in each instance, the E326K mutation was found on the same allele with another glucocerebrosidase mutation. Utilizing polymerase chain reaction (PCR) screening and restriction digestions of both patients with Gaucher disease and normal controls, we identified the E326K allele in both groups. Of the 310 alleles screened from patients with Gaucher disease, the E326K mutation was detected in four alleles (1.3%). In addition, screening for the E326K mutation among normal controls from a random population revealed that three alleles among 316 screened (0.9%) also carried the E326K mutation. In the normal controls with the E326K allele, the glucocerebrosidase gene was completely sequenced, but no additional mutations were found. Because the E326K mutation may be a polymorphism, we caution that a careful examination of any allele with this mutation should be performed to check for the presence of other glucocerebrosidase mutations.

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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)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.873
Threshold uncertainty score0.420

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.002
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 head0.119
GPT teacher head0.406
Teacher spread0.287 · 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