A novel exon 3 mutation (D76V) in the SOD1 gene associated with slowly progressive ALS

Abstract

Details of the mutations in the Cu/Zn superoxide dismutase (SOD1) gene in patients with the familial form of amyotrophic lateral sclerosis are currently being gathered in order better to understand the genotype-phenotype relationship in this disorder. We report on a large family with 15 affected individuals spanning five generations. A novel mutation in the exon 3 of the SOD1 gene, an A-to-T transversion at nucleotide position 696 in the heterozygous state leading to a D76V amino acid change, was identified in four family members. Affected individuals showed a homogeneous phenotype, characterized by initial symptoms in the lower limbs, clinical onset in the fifth decade of life, long survival and high penetrance. Our results are discussed in relation to the previously reported exon 3 SOD1 mutations, paying particular attention to the phenotypic characteristics of ALS-SOD1 patients.