Abstract
Mutations in the profilin 1 (PFN1) gene, encoding a protein regulating filamentous actin growth through its binding to monomeric G-actin, have been recently identified in familial amyotrophic lateral sclerosis (ALS). Functional studies performed on ALS-associated PFN1 mutants demonstrated aggregation propensity, alterations in growth cone, and cytoskeletal dynamics. Previous screening of PFN1 gene in sporadic ALS (SALS) cases led to the identification of the p.E117G mutation, which is likely to represent a less pathogenic variant according to both frequency data in control subjects and cases, and functional experiments. To determine the effective contribution of PFN1 mutations in SALS, we analyzed a large cohort of 1168 Italian SALS patients and also included 203 frontotemporal dementia (FTD) cases because of the great overlap between these 2 neurodegenerative diseases. We detected the p.E117G variant in 1 SALS patient and the novel synonymous change p.G15G in another patient, but none in a panel of 1512 control subjects. Our results suggest that PFN1 mutations in sporadic ALS and in FTD are rare, at least in the Italian population.