TARDBP and amyotrophic lateral sclerosis: Of note, a WGS analysis performed on pathologically confirmed Frontotemporal Lobar Degeneration-TDP-43 patients, negative for C9orf72 and GRN mutations, revealed a heterozygous missense mutation in TBK1 in three patients and a loss-of-function mutation in TBK1 associated with deletion of exons 13–15 of OPTN [61], thereby corroborating the idea of an oligogenic model of disease in the ALS–FTD spectrum caused by multiple rare variants with additive or synergistic effects on disease presentation (i.e., both TBK1 and OPTN are involved in the autophagy pathways) [12].