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

BACKGROUND
•Adult ataxia is a progressive neurodegenerative disorder characterized by impaired coordination of muscle movements with features including unsteadiness, incoordination, slurred speech, and oculomotor abnormalities.
• The diagnostic yield for adult ataxia by next-generation sequencing is over 30%. However, other testing methodologies are thought to be able to increase this yield further.
• Recent progress with long-read sequencing has identified a deep intronic GAA expansion in FGF14 as a cause of late-onset spinocerebellar ataxia 27B (SCA27B). This large FGF14 repeat expansion poses detection challenges for short-read sequencing.
• This FGF14 expansion may be present in 10-30% of European and Indian cohorts of patients with unsolved adult-onset ataxia, and could be as high as 60% in French-Canadian patients from Quebec.
• We present molecular findings from a clinical WGS cohort and a general population cohort to further characterize the allelic architecture and phenotypic correlation of this genetic cause of adult ataxia.