title: Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with a positive familial history in 5-10% of ALS cases. Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS. Here we report a novel mutation in exon 4 of SOD1 gene in a 55-year-old ALS patient belonging to a large Italian family with ALS first clinically described in 1968. In the family the clinical presentation was characterized by relatively early age of onset, spinal onset with proximal distribution weakness, bulbar involvement and a rapid disease course. Molecular analysis showed a heterozygous mutation at codon 106 resulting in a substitution of phenylalanine for leucine in the SOD1 protein (L106F). In analogy with the previously reported L106V mutation, we propose that the L106F causes a relevant destabilization of the protein chain around the mutation site, able to affect the SOD1 monomer and dimer structures suggesting a pathogenic role for this novel mutation.
authors.affiliation: Department of Neuroscience, University of Siena, Siena, Italy. battistinis@unisi.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Battistini
authors.forename: Claudia
authors.initials: C
authors.lastname: Ricci
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Lotti
authors.forename: Michele
authors.initials: M
authors.lastname: Benigni
authors.forename: Stella
authors.initials: S
authors.lastname: Gagliardi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucco
authors.forename: Massimo
authors.initials: M
authors.lastname: Bondavalli
authors.forename: Norina
authors.initials: N
authors.lastname: Marcello
authors.forename: Mauro
authors.initials: M
authors.lastname: Ceroni
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010649:Phenylalanine / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D010649:Phenylalanine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000409:Alanine