Expression of Parkinson's disease and associated neurophenotypes in 22q11.2 deletion syndrome
Bibliographic record
Abstract
The etiology of Parkinson’s disease (PD) remains largely unknown with the exception of a few genetic mutations that affect a small proportion of patients. Case reports suggest that individuals with 22q11.2 deletion syndrome (22q11.2DS), a multisystem genomic disorder associated with hemizygous 22q11.2 deletions, may be at increased risk of early-onset PD. The aim of this thesis was to investigate 22q11.2 deletions as a risk factor for early-onset PD. The prevalence of PD was assessed in a well-characterized cohort of adults with 22q11.2DS. Neuropathological studies were performed in cases with available post-mortem tissue. Whole-genome sequencing was used to investigate the possible contribution of genome-wide rare coding mutations to disease penetrance in neuropathologically confirmed PD cases. Assessment of putative pre-diagnostic clinical and neuroimaging markers of PD in a subset of the older adults (30 to 54 years) provided evidence of an elevated prevalence of pre-morbid motor and olfactory deficits, and of nigrostriatal dopaminergic dysfunction assessed using 11C-dihydrotetrabenazine and positron emission tomography. The clinical context of early-onset PD in this adult cohort of individuals with 22q11.2DS was also investigated. Treatment response was excellent to the atypical antipsychotic, clozapine, a candidate for use in psychotic patients at risk of, or with, PD. Cognitive level and severe psychiatric disorders were mediators of baseline functional capacity in 22q11.2DS adults. Practical guidelines were developed from a review of the 22q11.2DS literature to help inform the management of 22q11.2DS-associated conditions, including PD. The results of these studies provided evidence that early-onset PD is associated with the 22q11.2 deletion with important implications for PD pathogenesis and for the clinical management of 22q11.2DS.
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 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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".