Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene.
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.
Battistini
Stefania
S
Department of Neuroscience, University of Siena, Siena, Italy. battistinis@unisi.it
Ricci
Claudia
C
Lotti
Enrico Maria
EM
Benigni
Michele
M
Gagliardi
Stella
S
Zucco
Riccardo
R
Bondavalli
Massimo
M
Marcello
Norina
N
Ceroni
Mauro
M
Cereda
Cristina
C
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
C000606290:SOD1 protein, human; D010649:Phenylalanine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000409:Alanine