title: Copper/zinc superoxide dismutase 1 and sporadic amyotrophic lateral sclerosis: analysis of 155 cases and identification of a novel insertion mutation.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in the brain and spinal cord and leading to death within 5 years of symptom onset. The great majority of ALS cases are sporadic, with the familial form (FALS) representing fewer than 10% of all cases. Mutations in the copper/zinc superoxide dismutase 1 (SOD-1) gene have previously been identified as the underlying cause of approximately 20% of FALS cases. As the familial and sporadic forms of the disease are clinically similar, we have sought to determine whether such mutations in SOD-1 underlie any sporadic ALS cases. We have screened 155 sporadic cases by single-strand conformation polymorphism and have identified 4 sporadic cases that possess point mutations in exon 4 of the SOD-1 gene. Two of these mutations are identical to those previously reported in FALS cases. One mutation is novel, resulting in a frameshift at Val118 due to the replacement of G (first base in the last codon of exon 4) by AAAAC. This mutation results in a truncated SOD-1 protein due to the introduction of a stop codon three residues into exon 5.
authors.affiliation: Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jackson
authors.forename: A
authors.initials: A
authors.lastname: Al-Chalabi
authors.forename: Z E
authors.initials: ZE
authors.lastname: Enayat
authors.forename: B
authors.initials: B
authors.lastname: Chioza
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
authors.forename: K E
authors.initials: KE
authors.lastname: Morrison
mesh_terms: D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase