Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD1) cause approximately 20% of familial ALS. One of the possible mechanisms whereby they induce disease is mitochondrial dysfunction in motor neurons. Here we describe a patient with ALS and muscle mitochondrial oxidative defect associated with a novel SOD1 mutation. Direct sequencing of SOD1 gene revealed a heterozygous mutation in codon 22 substituting a highly conserved amino acid, from glutamine to arginine (Q22R). Muscle biopsy showed a neurogenic pattern associated with cytochrome c oxidase (COX) deficiency in several muscle fibers. Western blot analysis demonstrated a reduction in SOD1 content in the cytoplasmic and mitochondrial fractions. These results suggest that a minute quantity of mutant SOD1 protein contributes to a mitochondrial toxicity also in muscle tissue.
Corti
Stefania
S
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
Donadoni
Chiara
C
Ronchi
Dario
D
Bordoni
Andreina
A
Fortunato
Francesco
F
Santoro
Domenico
D
Del Bo
Roberto
R
Lucchini
Valeria
V
Crugnola
Veronica
V
Papadimitriou
Dimitra
D
Salani
Sabrina
S
Moggio
Maurizio
M
Bresolin
Nereo
N
Comi
Giacomo P
GP
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000235:genetics / Q000473:pathology; D001120:Arginine / Q000235:genetics; D045304:Cytochromes c / Q000378:metabolism; D004252:DNA Mutational Analysis; D005192:Family Health; D008040:Genetic Linkage / Q000502:physiology; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000473:pathology* / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000209:etiology*; D009154:Mutation / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D018698:Glutamic Acid; D045304:Cytochromes c; D001120:Arginine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1