Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction

作者：Corti Stefania; Donadoni Chiara; Ronchi Dario; Bordoni Andreina; Fortunato Francesco; Santoro Domenico; Del Bo Roberto; Lucchini Valeria; Crugnola Veronica; Papadimitriou Dimitra; Salani Sabrina; Moggio Maurizio; Bresolin Nereo; Comi Giacomo P^*

来源：Journal of the Neurological Sciences, 2009, 276(1-2): 170-174.

DOI：10.1016/j.jns.2008.09.030

• Amyotrophic lateral sclerosis
• Motor neuron
• Mitochondria
• SOD1

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.

• 出版日期2009-1-15