The strongestclinical, brain histopathology and functional overlap is observed for VCP,OPTN, SQSTM1 and UBQLN2 genes, suggesting that thesegenes represent the core of the disease continuum.21 Intriguingly, mutations in three of these(VCP, OPTN and SQSTM1) cause Paget disease, inaddition to ALS and FTD. This evidence concerns the gene SQSTM1 and frontotemporal dementia.