Pathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions.

ABSTRACT: Fused in sarcoma (FUS) is an RNA-binding protein implicated in juvenile amyotrophic lateral sclerosis (ALS). Mutations in the FUS gene, particularly those affecting the nuclear localization signal (NLS), impair nuclear import and lead to cytoplasmic accumulation of FUS inclusions in motor neurons. However, the pathological and clinical significance of FUS variants outside the NLS remains less understood. Here, we describe clinical and histopathological findings from three ALS patients carrying FUS variants: two with NLS-region variants (R495X and P525L), and one with a variant in the N-terminal region outside the NLS (Q23L). The patients carrying NLS variants presented with aggressive, juvenile-onset spinal and bulbar ALS, characterized primarily by lower motor neuron involvement and rapid

SUBMITTER: Stenvall E 

PROVIDER: S-EPMC12409623 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature