title: Identification of three novel mutations in the gene for Cu/Zn superoxide dismutase in patients with familial amyotrophic lateral sclerosis.
abstract: About 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord, exhibit autosomal dominant inheritance. A subgroup of these familial cases are caused by mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). We report here three additional mutations occurring in the SOD1 gene in three families with ALS. Two of these changes are missense mutations in exon 5 of the SOD1 gene, resulting in leucine 144 to serine and alanine 145 to threonine substitutions. The third, a single base pair change in intron 4 immediately upstream of exon 5, results in an alternatively spliced mRNA. The alternate transcript conserves the open reading frame of exon 5, producing an SOD1 protein with three amino acids inserted between exons 4 and 5 (following residue 118). These three mutations bring to 29 the total number of distinct SOD1 mutations associated with familial ALS.
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005799:Genes, Dominant; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase