“…The application of next generation sequencing, either in the form of targeted, whole exome or whole genome sequencing (WGS) has had a significant impact on the identification of genes associated with these diseases. However, it is also: (i) broadening the range of diseases that we see associated with variants in these genes ( Table 2), (ii) broadening the range of genes that you would conventionally associate with ALS and FTD (Blauwendraat et al, 2018;Tripolszki et al, 2019), (iii) increasing the frequency of variants in known ALS and FTD genes within apparently sporadic cases, highlighting the variable penetrance of many of these proposed mutations (Tripolszki et al, 2019), (iv) identifying multiple variants in disease-associated genes within an individual (Cady et al, 2015), which will become increasingly important as personalized medicine based on your genetic mutation enters the clinic and finally (v) illustrating both the variability in frequencies of known genes across populations worldwide (Majounie et al, 2012;Wei et al, 2019), but also the inequality as the majority of these studies are undertaken in the northern hemisphere. It is hoped that WGS of large international cohorts of ALS and FTD such as Project MinE 2 and GENFI 3 will begin to fully understand the genetic contribution to disease and potentially answer why individuals with a particular variant go on to develop ALS, FTD or ALS-FTD.…”