Hereditary Spastic Paraplegia
Bibliographic record
Abstract
BACKGROUND: Autosomal dominant hereditary spastic paraplegia (ADHSP) is mainly caused by mutations in the SPG4 gene, which encodes a new member of the AAA (adenosine triphosphatases associated with diverse cellular activities) protein family (spastin). Accumulation of genotype-phenotype correlation is important for better understanding of SPG4-linked hereditary spastic paraplegia. OBJECTIVES: To perform a clinical and genetic study of families with ADHSP and to perform the functional analysis of the founder mutation discovered in the SPG4 gene. DESIGN: Genetic and clinical study. Patients Fifteen unrelated families with ADHSP originating from southern Scotland. MAIN OUTCOME MEASURES: Clinical assessment, linkage analysis, haplotype study, expression of mutant spastin protein in cultured cells. RESULTS: Nine families with ADHSP were linked to the SPG4 locus at 2p21-p24. Sequence analysis of SPG4showed a novel N386S mutation in all 9 of these families. Expression of mutant spastin showed aberrant distribution in cultured cells. Haplotype analysis suggested the existence of a common founder. Clinical examination of the affected members carrying the mutation showed phenotypic variations including broad range of age at onset and disease duration and additional neurologic features such as mental retardation. Magnetic resonance imaging demonstrated unique features, including thin corpus callosum and atrophy of the cerebellum in 2 patients. Linkage and sequence analyses showed no evidence of linkage to the currently known ADHSP loci in the remaining 6 families. CONCLUSIONS: A founder SPG4 mutation N386S was identified in the families with ADHSP originating from southern Scotland. Clinical investigation showed intrafamilial and interfamilial phenotypic variations. The genetic study demonstrated evidence of further genetic heterogeneity in ADHSP.
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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) | 0.001 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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".