This is strikingly true of the two commonest ALS genes, SOD1 and C9ORF72, where the proportion of mutation carriers with no family history may be as high as 50% and 85%, respectively.23 These typically represent previously unrecognised familial cases due to an incomplete family history rather than de novo mutations, although this can occur, as seen in the case of SOD1. Here, SOD1 is linked to amyotrophic lateral sclerosis.