A New Variant Cu/Zn Superoxide Dismutase (Val7→Glu) Deduced from Lymphocyte mRNA Sequences from Japanese Patients with Familial Amyotrophic Lateral Sclerosis

Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis

“…17,18 The patients had a diagnosis of probable or possible ALS as defined in the revised El Escorial diagnostic criteria. The study group comprised 61 Japanese patients with sporadic or familial ALS, who had no mutations in SOD1, FUS, TARDBP, OPTN, C9ORF72, or UBQLN2 gene.…”

Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: correlation between genotype and clinical features.

“…Activity of CuZnSOD in patients with familial ALS with some CuZnSOD mutations is reduced to 25%-80% of normal in red blood cells," 16 17 40 73 74 fibroblasts,2' and brain40 75 (fig 4). In some patients, however, the mutant dimer may have a dominant negative effect on the activity and longevity of the wildtype subunit48 although this is an exception rather than a rule, and the activity of CuZnSOD in red blood cells of patients with ALS homozygous for the Asp9OAla mutation is essentially normal.23…”

Decreased thermal stability of red blood cellglu100→gly superoxide dismutase from a family with amyotrophic lateral sclerosis

“…ever, mean activities of 65-80% have subsequently been measured for other mutants [10,11,16] and we have found activities with the glu ~°°---> gly mutant to be ~ 80% of normal [4]. While it is not known how mutations in SOD give rise to FALS, available information favours a mechanism involving a gain in function.…”

“…Studies with recombinant mutant SODs have shown that some but not others have a decreased specific activity [5][6][7]. Similarly, in red cells of affected individuals, SOD activity varies from 30% normal to within the normal range [2,[8][9][10][11] and both active mutant homoand heterodimers of a charge change variant can be detected [4]. These observations, in conjunction with the finding that transgenic mice expressing FALS mutant as well as their normal SOD develop motor neuron disease [12,13], are strong evidence that a gain in function rather than a loss of ability to dismutate superoxide is responsible for the disease.…”