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

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. 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. 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. One genetically confirmed case of SCA27B was identified, corresponding to a frequency of 0.6% (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. 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 illustrates the allelic diversity of the FGF14 GAA locus. These findings highlight the importance of investigating diverse populations to better understand the genetic mechanisms underlying SCA27B and other repeat expansion-associated ataxias.