An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.

ABSTRACT: Adult-onset cerebellar ataxias are a group of neurodegenerative conditions that challenge both genetic discovery and molecular diagnosis. In this study, we identified an intronic (GAA) repeat expansion in fibroblast growth factor 14 (FGF14). Genetic analysis of 95 Australian individuals with adult-onset ataxia identified four (4.2%) with (GAA)_>300 and a further nine individuals with (GAA)_>250. PCR and long-read sequence analysis revealed these were pure (GAA) repeats. In comparison, no control subjects had (GAA)_>300 and only 2/311 control individuals (0.6%) had a pure (GAA)_>250. In a German validation cohort, 9/104 (8.7%) of affected individuals had (GAA)_>335 and a further six had (GAA)_>250, whereas 10/190 (5.3%) control sub

SUBMITTER: Rafehi H 

PROVIDER: S-EPMC9892775 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature