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FGF14 (GAA∙TTC) repeat expansion-related ataxia SCA27B is common in Northern Finland

2025· article· en· W4411985855 on OpenAlexaff
Laura Kytövuori, David Pellerin, Mikko Kärppä, Jussi Sipilä, Marie-Josée Dicaire, Pablo Iruzubieta, Bernard Brais, Kari Majamaa

Bibliographic record

VenueParkinsonism & Related Disorders · 2025
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersOulun Yliopistollinen Sairaala
KeywordsAtaxiaTrinucleotide repeat expansionNeuroscienceMedicinePsychologyBiologyGeneticsAllele

Abstract

fetched live from OpenAlex

Introduction An intronic repeat expansion (GAA∙TTC) exp in the FGF14 gene ( FGF14 (GAA∙TTC) exp ) has recently been found to cause dominantly inherited ataxia SCA27B. The core phenotype consists of late-onset and slowly progressing ataxia with down-beat nystagmus and episodic features. Disease penetrance depends on the number of repeat units and ≥ 300 is widely used pathogenic threshold for complete penetrance. The Finnish population is genetically unique and SCA27B has not previously been reported in Finland. Methods We investigated FGF14 (GAA∙TTC) exp in a cohort of 96 Finnish patients with suspected hereditary ataxia or ataxia of unknown etiology, of whom 62 patients had no previous genetic diagnosis. We also assessed FGF14 (GAA∙TTC) exp in 561 controls in order to estimate its population prevalence in North Ostrobothnia. Results We found five patients with FGF14 (GAA∙TTC) ≥250 giving a frequency of 5.2 % in the ataxia cohort. One patient had a rare biallelic genotype. Four patients had the classical SCA27B phenotype with no atypical features. Two of the patients had a previous genetic diagnosis and digenic contribution could not be excluded. Moreover, we found one patient with suspected FGF14 disease and with (GAA∙TTC) 248 , but the segregation analysis remained inconclusive. The (GAA∙TTC) ≥250 frequency was 2.7 % in the general population. Population prevalence was 1.7 per 100 000 in North Ostrobothnia. The frequency of alleles harboring 200‒249 repeats was 2.2 % in patients and 1.5 % in controls. Conclusion Our results suggest that screening of FGF14 expansion should be carried out in Finnish patients with suspected hereditary ataxia or ataxia of unknown etiology.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.024
Threshold uncertainty score0.047

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.010
GPT teacher head0.253
Teacher spread0.243 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations1
Published2025
Admission routes1
Has abstractyes

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