De novo nonsense mutation of the FUS gene in an apparently familial amyotrophic lateral sclerosis case.

Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes.