SCA27B_FGF14
- Gene
- FGF14
- Disease
- SCA27B
- Inheritance
- AR
- Classification
- Definitive
- Total Score
- 13.5
- Publications Reviewed
- 6
- Publication Span
- 22.41 years
- Last Updated
- 06/04/2025
- Curator(s)
- Laurel Hiatt, Harriet Dashnow
Description
SCA27B/ATX-FGF14 is associated with a pathogenic intronic GAA repeat expansion in FGF14, with cohort data supporting a fully pathogenic range for larger expansions and reduced penetrance for intermediate alleles. Affected individuals typically present with adult-onset, slowly progressive cerebellar ataxia, often with episodic features, gait/balance impairment, ocular motor findings, and cerebellar pathology. Supporting experimental evidence includes FGF14 gene-level mouse and protein-interaction studies.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:36493768 | 6 | Thirteen Australian individuals with adult-onset cerebellar ataxia carried pure intronic FGF14 (GAA)>250 expansions by LR-PCR/RP-PCR; eight had genome-sequence support and five were further characterized by long-read sequencing. |
| Collective Evidence | Allele | PMID:39263992 | 2 | In 102 genetically confirmed SCA27B patients, the expanded allele had median size 337 repeats (maximum 521), and larger repeat size was associated with younger age at disease onset. |
| Collective Evidence | Segregation | PMID:12489043 | 0.5 | Gene-level evidence only: linkage in an autosomal dominant ataxia family mapped to chromosome 13q34 with maximum LOD score 4.28 at D13S280 and identified FGF14 F145S; not specific to the intronic GAA SCA27B repeat locus. Score was downgraded to 0.5 as the evidence is not specific to the repeat expansion. |
| Statistics | Case-control data | PMID:36516086 | 6 | The FGF14 (GAA)≥250 repeat expansion was significantly associated with late-onset cerebellar ataxia in two independent case–control cohorts: 66 patients and 209 controls in the French Canadian group, and 228 patients and 199 controls in the German group. Odds ratios were 105.60 (CI: 31.09–334.20) and 8.76 (CI: 3.45–20.84), respectively, with P-values <0.001 in both cohorts. |
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Experimental evidence
Total: 1.5
| Models | Non-human model organism | PMID:12123606 | 1 | Gene-level model only: Fgf14-deficient mice were viable but developed ataxia and paroxysmal hyperkinetic dyskinesia with reduced dopamine-agonist responses. This gene-level evidence supports the role of FGF14 in ataxia but is not specific to the intronic GAA SCA27B repeat locus. |
| Function | Protein interaction | PMID:17978045 | 0.5 | Gene-level variant evidence only: FGF14 F145S reduced Nav channel localization at the axon initial segment, attenuated sodium currents, and disrupted wild-type FGF14 interaction with Nav alpha subunits. This gene-level evidence supports the role of FGF14 in ataxia but is not specific to the intronic GAA SCA27B repeat locus. |
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Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.