Very Low Frequency of SCA27B Among Undiagnosed Cerebellar Ataxia Patients in Peru

Background: Spinocerebellar ataxia type 27B (SCA27B) is a recently described autosomal dominant ataxia caused by a pathogenic GAA repeat expansion in the FGF14 gene. The frequency and the distribution of FGF14 repeat alleles remain largely unexplored in underrepresented populations, particularly in Latin America. Objective: To investigate the frequency of SCA27B and characterize the allelic distribution of the GAA- FGF14 microsatellite locus in a Peruvian cohort of individuals with ataxia of unknown molecular etiology. Methods: We analysed a cohort of affected individuals evaluated at a referral center for neurogenetic disorders in Peru. All individuals underwent standardized neurological assessment, as well as molecular analysis of the GAA- FGF14 repeat locus using repeat-primed and long-range PCR-based approaches. Results: One genetically confirmed case of SCA27B was identified, corresponding to a frequency of 0.59% (1/167) in this cohort. Most alleles (91.61%) were within the non-pathogenic range (<250 repeats), 85.3% of them with less than 30 repeats. Notably, 16.17% of individuals carried non-GAA-pure expanded alleles with a complex [(GAA) _n (GCA) _m ] _z repeat structure, currently considered non-pathogenic. These alleles were not associated with a typical SCA27B phenotype. Conclusions: SCA27B appears to be a rare cause of hereditary ataxia in the Peruvian population. The high prevalence of non-GAA-pure expanded alleles and the distinct FGF14 allelic distribution suggest population-specific genetic variability, possibly influenced by Native American ancestry. These findings highlight the importance of investigating diverse populations to better understand the genetic mechanisms underlying SCA27B and other repeat expansion-associated ataxias.