Japanese familial amyotrophic lateral sclerosis family with a two‐base deletion in the superoxide dismutase‐1 gene

Abstract

The clinical characteristics of members of a familial amyotrophic lateral sclerosis (FALS) family from Oki Island, whose members have a 2‐bp deletion at codon 126 of Cu/Zn superoxide dismutase (SOD1) gene, are presented here. Mean age of the onset in the members was 42 years. Mean disease duration among the members who had not been placed on a respirator was approximately 2 years. Long‐term survivors with respiratory support presented disturbances in eye movement and urination toward the end stages of the disease. They predominantly exhibited lower motor neuron symptoms. In addition, the authors focused on frameshift, nonsense and non‐amino‐acid‐altering mutations. Frameshift and nonsense mutations were all found within exon 4, exon 5 and intron 4. These amyotrophic lateral sclerosis cases were likely to have shorter disease duration than the FALS patients with single substitution. Several hypotheses were presented on the pathogenesis of FALS with SOD1 mutation.