The <i>FGF14</i> GAA repeat expansion is a major cause of ataxia in the Cypriot population
Bibliographic record
Abstract
Abstract Dominantly inherited intronic GAA repeat expansions in the fibroblast growth factor 14 gene have recently been shown to cause spinocerebellar ataxia 27B. Currently, the pathogenic threshold of (GAA)≥300 repeat units is considered highly penetrant, while (GAA)250–299 is likely pathogenic with reduced penetrance. This study investigated the frequency of the GAA repeat expansion and the phenotypic profile in a Cypriot cohort with unresolved late-onset cerebellar ataxia. We analysed this trinucleotide repeat in 155 patients with late-onset cerebellar ataxia and 227 non-neurological disease controls. The repeat locus was examined by long-range PCR followed by fragment analysis using capillary electrophoresis, agarose gel electrophoresis and automated electrophoresis. A comprehensive comparison of all three electrophoresis techniques was conducted. Additionally, bidirectional repeat-primed PCRs and Sanger sequencing were carried out to confirm the absence of any interruptions or non-GAA motifs in the expanded alleles. The (GAA)≥250 repeat expansion was present in 12 (7.7%) patients. The average age at disease onset was 60 ± 13.5 years. The earliest age of onset was observed in a patient with a (GAA)287 repeat expansion, with ataxia symptoms appearing at 25 years of age. All patients with spinocerebellar ataxia 27B displayed symptoms of gait and appendicular ataxia. Nystagmus was observed in 41.7% of the patients, while 58.3% exhibited dysarthria. Our findings indicate that spinocerebellar ataxia 27B represents the predominant aetiology of autosomal dominant cerebellar ataxia in the Cypriot population, as this is the first dominant repeat expansion ataxia type detected in this population. Given our results and existing research, we propose including fibroblast growth factor 14 GAA repeat expansion testing as a first-tier genetic diagnostic approach for patients with late-onset cerebellar ataxia.
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 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 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".