Genetic testing for SCA27B in Korean Multiple System Atrophy

FGF14 (GAA) _n repeat expansions are a common cause of idiopathic late-onset ataxia (SCA27B). The cerebellar form of multiple system atrophy (MSA) has comparable clinical features, albeit faster progression. Hence, we performed an analysis of FGF14 genomic variability in a South Korean cohort of 199 patients with ‘probable’ MSA, compared with 1,048 ethnically-matched controls. All whole genome sequences (WGS) are depicted on a computational genome analysis platform, CGAP, to enable storage, visualization and analysis for partners of the International MSA Coalition. The size of the FGF14 (GAA) _n repeat was also assessed by genomic PCR, and by interrogating WGS data using Expansion Hunter (EH) with an extensive catalogue of potential repeats. However, MSA samples were not significantly different to matched Korean controls, and only three MSA patients showed possible abnormal FGF14 (GAA) _n expansions >300bp. Nevertheless, as PCR and EH findings were often discordant, a subset of samples with expansions was validated by long-read sequencing. Some intermediate expansions (>150 bp) were found in 6.9% (27/392) of controls compared to 13.4% (46/344) in MSA, though overall our results suggest FGF14 (GAA) _n repeat expansions do not influence susceptibility to MSA in Korean patients and highlight challenges inherent in this genetic testing.