title: FUS mutations in sporadic amyotrophic lateral sclerosis: clinical and genetic analysis.
abstract: Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with 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.523+3ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes.
authors: Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
authors: William
authors: W
authors: Sproviero
authors: Vincenzo
authors: V
authors: La Bella
authors: Rosalucia
authors: R
authors: Mazzei
authors: Paola
authors: P
authors: Valentino
authors: Carmelo
authors: C
authors: Rodolico
authors: Isabella Laura
authors: IL
authors: Simone
authors: Giancarlo
authors: G
authors: Logroscino
authors: Carmine
authors: C
authors: Ungaro
authors: Angela
authors: A
authors: Magariello
authors: Alessandra
authors: A
authors: Patitucci
authors: Gioacchino
authors: G
authors: Tedeschi
authors: Rossella
authors: R
authors: Spataro
authors: Francesca
authors: F
authors: Condino
authors: Francesco
authors: F
authors: Bono
authors: Luigi
authors: L
authors: Citrigno
authors: Maria Rosaria
authors: MR
authors: Monsurrò
authors: Maria
authors: M
authors: Muglia
authors: Antonio
authors: A
authors: Gambardella
authors: Aldo
authors: A
authors: Quattrone
authors: Francesca Luisa
authors: FL
authors: Conforti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: D034702:RNA-Binding Protein FUS