Glucocerebrosidase Mutations in a French-Canadian Parkinson's Disease Cohort
Bibliographic record
Abstract
Gaucher disease is a rare Mendelian disorder characterized by mutations in lysosomal enzyme glucocerebrosidase (GBA) gene, leading to accumulation of the glycolipid glucosylceramide.At the present time, over 335 mutations have been reported in GBA, most of which are predicted to lead to loss of enzyme function (Human Gene Mutation Database, HGMD http://www.hgmd.cf.ac.uk/ac/index/.php).Gaucher Disease is divided into three types, based on the clinical symptoms and neurological manifestations: type 1 nonneuronopathic (MIM#230800); type 2 acute neuronopathic (MIM#230900) and type 3 subacute neuronopathic (MIM#231000); type 2 and 3 are the most severe forms.Recently, family studies showed an increased incidence of Parkinson's disease (PD) in relatives of patients with Gaucher disease, suggesting that haploinsufficiency of GBA may predispose to PD 1 .A multicenter analysis of GBA reported a higher frequency of missenses mutations in PD patients than in healthy control individuals 1 .Interestingly, this result was even more significant when only individuals of Jewish descent were considered; 15% of PD patients in this subgroup had either an L144P or a N370S mutation, which is five times higher than what can be observed in healthy controls of Jewish descent.In non-Jewish individuals the mutation frequency in PD patients was 3% which is significantly higher than in matched healthy controls, where it was less than 1%.This observation was subsequently replicated in a PD sample of Chinese origin, but not replicated in a North-African Berber-Arab Tunisian population of PD cases 2,3 .The goal of our study was to evaluate the possible involvement of the GBA mutations in a French-Canadian PD cohort.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.002 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".