title: Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction.
abstract: 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.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Chiara
authors.initials: C
authors.lastname: Donadoni
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Fortunato
authors.forename: Domenico
authors.initials: D
authors.lastname: Santoro
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucchini
authors.forename: Veronica
authors.initials: V
authors.lastname: Crugnola
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.forename: Sabrina
authors.initials: S
authors.lastname: Salani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: 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
chemical_list: C000606290:SOD1 protein, human; D018698:Glutamic Acid; D045304:Cytochromes c; D001120:Arginine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1