title: Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis.
abstract: Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by the death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS.
authors.affiliation: Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Hosler
authors.forename: G A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: P C
authors.initials: PC
authors.lastname: Sapp
authors.forename: W
authors.initials: W
authors.lastname: Chin
authors.forename: R W
authors.initials: RW
authors.lastname: Orrell
authors.forename: J S
authors.initials: JS
authors.lastname: de Belleroche
authors.forename: J
authors.initials: J
authors.lastname: Esteban
authors.forename: L J
authors.initials: LJ
authors.lastname: Hayward
authors.forename: D
authors.initials: D
authors.lastname: Mckenna-Yasek
authors.forename: L
authors.initials: L
authors.lastname: Yeung
authors.forename: A K
authors.initials: AK
authors.lastname: Cherryson
authors.forename: J E
authors.initials: JE
authors.lastname: Dench
authors.forename: S D
authors.initials: SD
authors.lastname: Wilton
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D005192:Family Health; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase