GAA-FGF14 Ataxia Is a Frequently Overlooked Cause of Sporadic Adult-Onset Ataxia.

Intronic GAA repeat expansion in FGF14, detectable only by long-range PCR or long-read sequencing

A German cohort of 107 genetically unresolved sporadic ataxia patients was tested by long-range PCR and Nanopore sequencing for GAA-FGF14 expansion (SCA27B). A diagnostic yield of 13% was observed (10% pathogenic expansion, 6% intermediate among sporadic cases), reaching 50% in cases with typical clinical features. This confirms SCA27B as a frequent and under-diagnosed cause of adult-onset cerebellar ataxia, undetectable by standard short-read NGS panels.

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This result strengthens the case for systematically including GAA-FGF14 expansion testing in the workup of unresolved adult-onset ataxia — as a complement to standard NGS panels. Long-read sequencing or targeted long-range PCR is emerging as the second-tier diagnostic tool in this indication.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 6/10