ATXN2 intermediate repeat expansions influence the clinical phenotype in frontotemporal dementia

Common genetic risk factors are associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Intermediate repeat expansions at the Ataxin-2 locus (ATXN2) are a risk factor for ALS and influence the phenotype. We assessed whether ATXN2 is a risk factor for FTD or modify clinical features in a data set of Italian patients. Three hundred sixty-eight unrelated FTD cases and 342 controls were enrolled. The frequency of intermediate CAG repeats in ATXN2 gene was not different comparing patients and controls. CAG repeats were interrupted by CAA in all patients carrying intermediate repeats. Interestingly, patients with an increased number of CAG repeats had an earlier onset of the disease than those without expansions (p = 0.011), and presented more frequently with parkinsonism (p = 0.010), and psychotic symptoms (p = 0.013) at disease onset. Our study does not support a major role of ATXN2 intermediate CAG expansions in predisposing to FTD but suggests that ATXN2 may act as a phenotype modifier.