Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD]) 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.
Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction / S. Corti, C. Donadoni, D. Ronchi, A. Bordoni, F. Fortunato, D. Santoro, R. Del Bo, V. Lucchini, V. Crugnola, D. Papadimitriou, S. Salani, M. Moggio, N. Bresolin, G.P. Comi. - In: JOURNAL OF THE NEUROLOGICAL SCIENCES. - ISSN 0022-510X. - 276:1-2(2009 Jan 15), pp. 170-174.
Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction
S. CortiPrimo
;D. Ronchi;A. Bordoni;F. Fortunato;D. Santoro;R. Del Bo;V. Lucchini;V. Crugnola;D. Papadimitriou;S. Salani;N. BresolinPenultimo
;G.P. ComiUltimo
2009
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD]) 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.Pubblicazioni consigliate
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