Identification of FGF14 GAA expansions in Polish patients with undiagnosed cerebellar ataxia – a preliminary study

Introduction: Spinocerebellar ataxia type 27B (SCA27B), caused by an intronic GAA repeat expansion in the FGF14 gene, has recently emerged as a major cause of late-onset cerebellar ataxia (LOCA). Its prevalence and clinical profile in Central and Eastern Europe remain largely unknown. Objective: To determine the frequency and phenotypic characteristics of FGF14 GAA·TTC repeat expansions, a large cohort of Polish patients with undiagnosed adult-onset cerebellar ataxia was investigated. Methods: We retrospectively analyzed 701 patients (age of onset ≥25 years) with adult-onset cerebellar ataxia of unknown etiology, previously tested negative for SCA1, SCA2, SCA3, SCA8, and RFC1 expansions. GAA·TTC repeat lengths were assessed using long-range and repeat-primed PCR. Expansions ≥250 repeats were classified as pathogenic. Clinical and MRI data were evaluated where available. A control group of 66 neurologically healthy individuals was also screened. Results: Pathogenic FGF14 expansions (≥250 repeats) were identified in 4.4% (31/701) of patients, including 23 with fully penetrant (≥300) and 8 with incompletely penetrant (250–299) alleles. No pathogenic expansions were found in controls. The mean age of onset was 49.8 years. Common symptoms included balance and gait disturbances, cerebellar syndrome, and episodic features such as diplopia. Cerebellar atrophy was present in 45% of patients with available MRI. No significant correlation between repeat length and age of onset was observed. Summary: Our findings confirm that FGF14 repeat expansions are an underrecognized cause of LOCA in Poland and support their inclusion in standard genetic testing for adult-onset ataxias. Further studies are warranted to better define penetrance and genotype–phenotype correlations.