GAA/FGF14 ataxia: an ode to the phenotype-first approach

GAA-FGF14 disease/spinocerebellar ataxia 27B (SCA27B) has been recently pinpointed as a frequent cause of late onset cerebellar ataxia (LOCA).1,2 The disease is caused by a heterozygous GAA trinucleotide expansion in the first intron of the fibroblast growth factor 14 (FGF14) gene. FGF14 regulates Purkinje cell firing by modulating the function of voltage-gated sodium channels. Intronic GAA expansions are likely to result in FGF14 haploinsufficiency.1 Current literature supports pathogenicity for expansions containing ≥250 uninterrupted GAA repeats (GAA≥250).