A clinicopathological study of a patient with familial amyotrophic lateral sclerosis associated with a two base pair deletion in the copper/zinc superoxide dismutase (SOD1) gene

Abstract

The recognition of mutations in the copper/ zinc superoxide dismutase (SOD1) gene in familial amyotrophic lateral sclerosis (FALS) has been a landmark in ALS research. We report a clinicopathological study of a female patient with FALS showing a two base pair deletion in exon 5 of the SOD1 gene. Her clinical course was rapid and she died 2 years after the onset. The SOD1 activity was down to 30% of the normal level. Western blot analysis did not reveal the mutant protein which was expected to be ∼2.4 kDa smaller than normal SOD1 protein in molecular mass. In contrast to the neuropathological findings of the previously reported cases showing the same mutation, our case was characterized by sparing of the dorsal column and the presence of only a modest number of intracytoplasmic eosinophilic inclusions showing weak or partial immunoreaction for neurofilament and negative reaction for SOD1. Thus, the same mutation in the SOD1 gene does not necessarily induce consistent pathological changes in the central nervous system.