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Approximately 10% of cases of amyotrophic lateral sclerosis (ALS) are familial with the remainder being sporadic. Known ALS genes combined (including superoxide dismutase 1, SOD1) only account for about 20% of familial ALS cases, or around 2% of all ALS cases. Frontotemporal dementia (FTD) is estimated to be associated with between 3% and 22% of cases of ALS and as many as half of ALS cases appear to have frontotemporal impairment (reviewed by Neumann and colleagues1). Families with comorbid ALS and FTD are increasingly being recognised, and linkage analysis has implicated loci on chromosome 9.1 Taken together, this strongly suggests that ALS and FTD share a common pathogenic basis. Indeed, clinical and pathological overlap has been demonstrated for these disorders.
Mutations in CHMP2B have been previously described in familial FTD.2 Recently, CHMP2B mutations were also described in two unrelated cases with ALS phenotypes, each with an apparent family history of ALS spectrum disorders.3
To further investigate the possible association of CHMP2B mutations with ALS, we conducted a mutation screen of cohorts with “classic” ALS, comprising 166 ALS families and 372 cases of sporadic ALS (all familial ALS were negative for the known ALS genes Superoxide dismutase …