Frequency of C9orf72 repeat expansions in amyotrophic lateral sclerosis: a Belgian cohort study

We determined the frequency of C9orf72 repeat expansions in a large cohort of Belgian patients with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS). In total, 119 patients with fALS from 62 kindreds, 471 patients with sALS, and 384 control subjects were included. A C9orf72 repeat expansion was found in 32 of 62 fALS pedigrees (51.6%), in 45 of 471 patients with sALS (9.6%), but in none of the control subjects. Compared with fALS of unknown etiology or fALS caused by mutations in other ALS-causing genes, C9orf72 repeat expansion carriers had a later age at onset (57.3 vs. 51.4 years; p = 0.0061), a higher proportion of bulbar onset (31.9% vs. 12.5%, p < 0.0001), and a reduced survival (29.4 vs. 67.7 months, p = 0.0003). In the sALS cohort, there were no significant differences in these disease characteristics between the C9orf72 repeat expansion carriers and the noncarriers. C9orf72 repeat expansions are a frequent cause of ALS in Belgium, and also in sALS patients. These results might justify genetic testing of C9orf72 in all ALS patients.