14 research outputs found
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 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.
\ua9 2011 Elsevier Inc. All rights reserved
Further evidence that D90A-SOD1 mutation is recessively inherited in ALS patients in Italy
Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported to cause adult-onset autosomal dominant
amyotrophic lateral sclerosis (FALS). In sporadic cases (SALS), de novo mutations in the SOD1 gene have occasionally
been observed. All the SOD1 mutations are autosomal dominantly inherited with the exception of D90A. To date, in Italy,
only two sporadic ALS cases carrying the D90A mutation have been reported in a homozygous state.We investigated for the
presence of this mutation in 169 unrelated ALS patients from southern Italy. The genetic analysis revealed three ALS
patients (1.8%) with mild phenotype carrying the homozygous D90A mutation