This is considered to be the first description of an autopsy case of FALS with an I104FSOD1 gene mutation, suggesting that combination of marked intra-familial clinical variability and multisystem degeneration with occurrence of CIs and SOD1-positive NCIs is a characteristic feature of FALS with this SOD1 gene mutation.
While it may be that FALS is a consequence of loss of SOD1 function, it is also possible that motor neuron death in this dominantly inherited disease occurs because the mutations confer an additional, cytotoxic function on the SOD1 protein.
Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis.
The results show a significant decrease in Cu,Zn SOD activity in affected and at risk FALS individuals as compared to FALS patients without mutations, SALS individuals, normal and neurological controls.
Several point mutations in the gene coding for human Cu,Zn superoxide dismutase have been reported as being responsible for familial amyotrophic lateral sclerosis (FALS).
Familial amyotrophic lateral sclerosis (FALS) has been linked in some families to dominant mutations of the SOD1 gene encoding Cu,Zn superoxide dismutase (Cu,ZnSOD).
The G41D mutation in the superoxide dismutase 1 gene is associated with slow motor neuron progression and mild cognitive impairment in a Chinese family with amyotrophic lateral sclerosis.
Many of the SOD1 mutations associated with FALS appear to increase the likelihood that the enzyme will perform either one of these potentially harmful functions resulting in increased hydroxyl radical formation or the addition of nitro groups to tyrosine residues within cellular proteins.
Dominant inheritance of point mutations in CuZn superoxide dismutase (SOD1) is the best characterized subset of familial amyotrophic lateral sclerosis (FALS) and accounts for some 20% of the known familial cases.