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

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.