We identified a novel missense mutation in the Cu/Zn superoxide dismutase (SOD1) gene in a 47-year-old woman with familial amyotrophic lateral sclerosis (ALS). The heterozygous mutation, in exon 1 of the SOD1 gene, is a GC to TT transversion in nucleotide positions 13 and 14 leading to an alanine 4 to phenylalanine (A4F) amino acid substitution. It was found in six family members. The effect of the A4F mutation was of similar severity to that of the A4V mutation. We discuss structural instability as a possible pathogenic mechanism in the case of this SOD1 mutation. The proband displayed upper motor neuron signs not observed in individuals with other codon 4 mutations. This could be because longer survival allows UMN dysfunction to become evident. We also provide a literature review.
Copyright © 2011 Elsevier B.V. All rights reserved.