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

6533b85efe1ef96bd12c08d2

RESEARCH PRODUCT

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

Luigi Citrigno Carmine Ungaro Francesca Condino William Sproviero Francesca Luisa Conforti Maria Rosaria Monsurrò Maria Muglia Carmelo Rodolico Antonio Gambardella 1 Isabella Simone Vincenzo La Bella Rosalucia Mazzei Aldo Quattrone Gioacchino Tedeschi Angela Magariello Francesco Bono Giancarlo Logroscino Paola Valentino Alessandra Patitucci Rossella Spataro

subject

Male Aging Population DNA Mutational Analysis Biology Gene mutation medicine.disease_cause Genetic analysis FUS gene Mutant protein ALS; FUS gene; mutation; sporadic medicine Missense mutation Humans Genetic Predisposition to Disease Amyotrophic lateral sclerosis education Aged Genetics Aged 80 and over Neurologic Examination Mutation education.field_of_study General Neuroscience Neurodegeneration Amyotrophic Lateral Sclerosis Exons Middle Aged ALS; FUS gene; Mutation; Sporadic medicine.disease Magnetic Resonance Imaging Settore BIO/18 - Genetica sporadic Mutation RNA-Binding Protein FUS Female Settore MED/26 - Neurologia Neurology (clinical)ALS Geriatrics and Gerontology Developmental Biology

description

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.52313ins[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. © 2011 Elsevier Inc. All rights reserved.

year	journal	country	edition	language
2012-01-01

10.1016/j.neurobiolaging.2011.10.005 http://hdl.handle.net/10447/64570