Elucidating the Diagnostic Yield and Allelic Characteristics of FGF14 Repeat Expansions in Adult Ataxia Through Whole Genome Sequencing

BACKGROUND
• Late-onset hereditary cerebellar ataxia (LOCA) is a group of progressive neurodegenerative disorders that remain challenging to manage without a molecular diagnosis. Even with modern next-generation sequencing, a up to 40% of adults with late-onset ataxia remain without a genetic answer.
• Recent discoveries have shifted this landscape – most notably with identification of the intronic GAA expansion in FGF14 as a cause of late-onset spinocerebellar ataxia 27B (SCA27B), which cohort studies now report as a common genetic cause and range from 10-60% among LOCA referrals.
• Due to the size of the expansion, unbiased screening for FGF14 GAA expansion has technical limitations. We present molecular findings from a clinical whole genome sequencing (WGS) cohort to further characterize the allelic architecture and phenotypic correlation of this genetic cause of adult ataxia.