A novel 10-base pair insertion mutation in exon 5 of the SOD1 gene in a Chinese family with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, fatal neurodegenerative disease. Several genes are associated with ALS. Copper-zinc superoxide dismutase 1 (SOD1) is one of the most commonly mutated genes in ALS, and more than 160 mutations in SOD1 have been reported. We reported a novel heterozygous insertion mutation that led to a frameshift and a premature termination at position 136 in exon 5 of the SOD1 gene (c.392_393insGCAAAGGTGG; p.N132Qfs*5) in a Chinese familial ALS pedigree. This mutation in the pedigree demonstrated an autosomal dominant pattern of inheritance and a phenotype characterized by an early onset (approximately 34 years old) with a relatively rapid course (approximately 2 years) and limb onset with respiratory involvement. The clinical feature of the p.N132Qfs*5 mutation was nearly identical to a previously reported mutation (Gly127insTGGG). Experiments in G127X mice demonstrated that the G127X mutation was pathogenic. SOD1 activity in the p.N132Qfs*5 mutation carriers in the family decreased significantly compared with normal family members. In conclusion, we identified a novel SOD1 mutation in an ALS family, which is an important addition to the catalog of SOD1 mutations in ALS.