Ataxin-2 polyQ expansions in FTLD-ALS spectrum disorders in Flanders-Belgian cohorts

Abstract There exists considerable clinical and pathological overlap between frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), which implies that these 2 neurodegenerative conditions share common pathogenic mechanisms. Recently, intermediate-length (27-33) polyglutamine (polyQ) expansions in ataxin-2 ( ATXN2 ) have been associated with increased risk for ALS, while expansions of > 34 repeats are known to cause spinocerebellar ataxia type 2 (Sca-2). We identified in 72 ALS patients one patient with a 33 polyQ expansion that was absent in 810 control individuals. This allele was also found in one patient with concomitant ALS-Sca-2. In contrast, in a Flanders-Belgian series of 270 FTLD and 22 FTLD-ALS patients, we found no association with intermediate-length polyQ expansions nor did we observe patient-specific long expansions in agreement with the recent observation in a screening of a substantial sized cohort of patients with diverse neurodegenerative brain diseases. Our results provide further support to the notion that ATXN2 associated polyglutamine amplification is specific to the ALS-end of the FTLD-ALS disease spectrum.