FUS MUTATIONS IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS: CLINICAL AND GENETIC ANALYSIS

Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited formof amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmicaccumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we haveperformed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patientscarrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic positionhave been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patientswith FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants(3=-untranslated region [UTR] variant, c.*41G.A; c.52313ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from withinour cohort. This study underlines the importance of population-based mutation screening of newly identified genes.© 2011 Elsevier Inc. All rights reserved.