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Record W4416571317 · doi:10.1002/mds.70128

A Complex <scp> <i>FGF14</i> </scp> ( <scp>TTC</scp> )/( <scp>TGC</scp> ) Repeat Expansion in Parkinson's Disease

2025· article· en· W4416571317 on OpenAlexaff
Xiaosheng Zheng, Zhidong Cen, Xinhui Chen, Fan Zhang, Chenxin Ying, Nan Jin, Peng Liu, Yilin Chen, Haotian Wang, Jiaxiang Li, Joanne Trinh, Joshua Laß, David Pellerin, Matt C. Danzi, Stephan Züchner, Bernard Brais, Shen‐Yang Lim, Ai Huey Tan, Azlina Ahmad‐Annuar, Dehao Yang, Lebo Wang, Zhiru Lin, Fei Xie, Bo Wang, Sheng Wu, Zhiyuan Ouyang, Piu Chan, Shen Hu, Christine Klein, Hou‐Feng Zheng, Chaodong Wang, Wei Luo

Bibliographic record

VenueMovement Disorders · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFibroblast Growth Factor Research
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Natural Science Foundation of ChinaDeutsche Forschungsgemeinschaft
KeywordsTrinucleotide repeat expansionDiseaseParkinson's diseaseDegenerative diseaseCentral nervous system diseaseMovement disordersClinical neurology

Abstract

fetched live from OpenAlex

BACKGROUND: Repeat expansions have been reported as genetic causes/risk factors of Parkinson's disease (PD). As a novel repeat expansion locus, the FGF14-SCA27B (GAA)•(TTC) repeat locus is unexplored in PD. METHODS: Utilizing genetic sequencing and various polymerase chain reaction (PCR) methodologies, pure and complex repeat expansions in FGF14 were detected in Asian PD patients. Targeted long-read sequencing was performed to investigate the detailed sequence composition of these repeat expansions. Case-control studies were further performed. RESULTS: repeat expansion was detected as the main expanded genotype in our discovery cluster. Using targeted long-read sequencing, these complex (TTC)/(TGC) repeat expansions were characterized as (TTC)exp(TGCTTC)exp(TGCTTCTTCTTCTTC)n(TTC)n alleles with four segments (Seg 1-4), and further classified into four genotypic patterns. Pattern 1 was mainly characterized by a (CTC) interruption in the Seg 1-(TTC)exp. Patterns 2-4 were characterized by different repeat length of Seg 1-(TTC)exp and Seg 3-(TGCTTCTTCTTCTTC)n. Case-control analysis revealed a significant enrichment of Pattern 4 (TTC)/(TGC) repeat expansion in PD compared with controls (P = 0.024, OR: 2.60, 95% CI: 1.07-7.23) in the discovery cluster. This significant association between Pattern 4 (TTC)/(TGC) repeat expansion and PD was confirmed in one of two replication clusters (P = 0.035, OR: 2.18, 95% CI: 0.95-4.53) and the meta-analysis across all three clusters (P = 0.015, OR: 1.75, 95% CI: 1.10-2.79). INTERPRETATION: We identified a unique complex (TTC)/(TGC) repeat expansion in FGF14 as a novel genetic risk factor of PD in the Asian population. © 2025 International Parkinson and Movement Disorder Society.

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 score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.011
GPT teacher head0.260
Teacher spread0.249 · 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".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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