Genetic Identification in Early Onset Parkinsonism among Norwegian Patients
Bibliographic record
Abstract
Abstract Background An initial diagnosis of Parkinson's disease (PD) is challenging, especially in patients who have early onset and atypical disease. A genetic etiology for parkinsonism, when established, ends that diagnostic odyssey and may inform prognosis and therapy. The objective of this study was to elucidate the genetic etiology of parkinsonism in patients with early onset disease (age at onset <45 years). Methods Whole‐exome sequencing, copy number variability, and short tandem repeat analyses were performed. The analyses were focused on genes previously implicated in parkinsonism and dystonia in patients with early onset parkinsonism. Genotype‐phenotype correlations were assessed using regression models. Results The patient cohort was characterized by early onset, slowly progressive parkinsonism with a mean age at onset of 39.2 ± 5.0 years (n = 108). By 10 years of disease duration, the mean Hoehn & Yahr stage was 2.6 ± 0.8, the mean Unified Parkinson's Disease Rating Scale, part III (motor part) score was 24.9 ± 12.1 (n = 83), and 30 patients were cognitively impaired at the last examination (Montreal Cognitive Assessment score ≤ 26). Ten patients with typical early onset PD harbored homozygous or compound heterozygous mutations phosphatase and tensin homolog‐induced putative kinase 1 (PINK1) (n = 4), parkin (PRKN) (n = 3), or the leucine‐rich repeat kinase 2 (LRRK2) c.6055 G to A transition (n = 3). In addition, 5 patients with more atypical disease were compound heterozygotes for the glucocerebrosidase gene (GBA) (n = 3) 1 was heterozygous for solute carrier family 2, member 1 (SLC2A1) and another carried a novel ataxin 2 (ATXN2) exon 1 duplication. In most patients, the cumulative mutational burden did not appear to contribute to age at onset or progression Conclusion In this clinical series, 15 patients (14%) carried mutations that were linked to monogenic parkinsonism. GBA carriers were most likely to suffer an earlier cognitive demise. Nevertheless, the etiology for most patients with early onset PD remains to be determined.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".