If DNA methylation appears first, it must happen well before the onset of symptoms; increased binding of mutant C9orf72 to trimethylated histone H3K9 was similarly present in two asymptomatic repeat carriers (28 and 30 years of age) and in patients already diagnosed with ALS or FTD (clinical information in online resource, Table 3). Here, C9orf72 is linked to frontotemporal dementia.