35 Of these, the finding of the p.R496X FUS in an Italian sALS patient36 is of particular interest since the same mutation has been found to cosegregate with fALS in small families in Germany,37 Great Britain and Sweden, mirroring what we here report for sALS/fALS with SOD1 mutations. Genomic de novo mutations have also been reported in single sALS cases in ATXN2, SS18L1, CHRM1, ERBB4, VCP and RAPGEF2 genes raising the question: how frequent are de novo mutations as a cause of ALS?38. The gene discussed is RAPGEF2; the disease is amyotrophic lateral sclerosis.