Parkinsonism in GTP cyclohydrolase 1 mutation carriers
Bibliographic record
Abstract
Sir, We read with great interest the article by Mencacci and colleagues (2014) reporting a significantly higher frequency of GTP cyclohydrolase 1 ( GCH1 ) variants in patients with Parkinson’s disease compared to controls. Whole-exome sequencing of a large case-control cohort showed that rare GCH1 coding variants are associated with a 7-fold increased risk of Parkinson’s disease. Heterozygous loss-of-function mutations in GCH1 , a crucial enzyme for dopamine production in nigrostriatal neurons (Kaufman, 1959; Nagatsu et al. , 1964), are the most common cause of DOPA-responsive dystonia (DRD) (Ichinose et al. , 1994). DRD is a rare hereditary disease characterized by childhood-onset, generalized dystonia and a dramatic long-lasting response to levodopa (Segawa et al. , 1976). The disease may also manifest in adulthood with parkinsonism as the sole or dominant clinical feature (Hjermind et al. , 2006; Momma et al. , 2009). GCH1 mutations have been shown to segregate in pedigrees with multiple individuals affected by isolated parkinsonism, a phenotype …
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".