Genotype–Phenotype Relations for the Dystonia-Parkinsonism Genes GLB1, SLC6A3, SLC30A10, SLC39A14, and PLA2G6: MDSGene Systematic Review
Bibliographic record
Abstract
The Movement Disorders Society recommends the DYT/PARK prefix for genes where dystonia and parkinsonism are prominent in approximately half or more of patients. This systematic review explores the genotype–phenotype correlations of GLB1, SLC6A3, SLC30A10, PLA2G6, and SLC39A14—recently classified as DYT SLC39A14 and historically linked to dystonia-parkinsonism. We searched PubMed and the Human Gene Mutation Database using standardized terms, including English-language, peer-reviewed publications up to February 2024. Following the MDSGene protocol, we extracted individual-level data on patients with biallelic pathogenic variants and at least one movement disorder. Features were marked “missing” if not explicitly reported. Of 1828 articles, 128 were eligible. We identified 386 patients and 262 variants. The median age at onset was 3 years for GLB1, 3 months for SLC6A3, 2.5 years for SLC30A10, 1.5 years for SLC39A14, and 16 years for PLA2G6. Missing data may reflect underreporting of negative findings. Case reports/serie, may bias toward atypical presentations. Our analysis showed dystonia-parkinsonism predominates in SLC6A3 and PLA2G6, while GLB1, SLC30A10, and SLC39A1 show predominantly dystonic phenotypes with a low frequency of parkinsonism. Ataxia was common in GLB1 and PLA2G6. Awareness of these phenotypes is essential for early diagnosis and intervention, particularly in treatable conditions like SLC30A10 or SLC39A14. The predominantly dystonic phenotype in GLB1, SLC30A10, and SLC39A14 suggest that the DYT prefix may be more appropriate, highlighting the need to reconsider their nomenclature, and the importance of systematic reviews.
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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 | 0.005 | 0.023 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.007 |
| Bibliometrics | 0.010 | 0.013 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".