TARDBP and amyotrophic lateral sclerosis: In fact, there are several reports of patients carrying ≥2 mutations of different ALS-related genes.22 In a study of 391 patients with ALS that assessed variants in 17 genes, 3.8% had variants in >1 gene.23 In that series, the burden of rare variants in known ALS genes significantly reduced the age at onset of symptoms.23,24 In the present series, 1 patient had both a C9orf72 expansion and a heterozygous mutation of the TARDBP gene, even though we assessed only 4 genes.