title: A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis.
abstract: Recently, several missense mutations in the Cu/Zn superoxide dismutase gene (SOD1) have been reported as a putative cause of chromosome-21q-linked familial amyotrophic lateral sclerosis (FALS). We have discovered a novel missense mutation (substitution of Thr for Ala4) in exon 1 (GCC to ACC) in two FALS patients from one Japanese FALS family. No mutations were found in 17 cases of sporadic ALS. The enzyme activity of recombinant fusion protein containing the Cu/Zn superoxide dismutase (SOD) with the Ala4-to-Thr mutation was significantly reduced in E. coli. On the other hand, in the expression system in insect cells using Baculovirus, the mutant SOD expressed an enzyme activity as high as wild-type SOD. These results suggest that the stability of SOD with the Ala4-to-Thr mutation is disrupted especially in the fusion protein. Autopsy was carried out on one of the two patients, and the pathological findings were typical of FALS with posterior column involvement. These results raise the possibility that mutation of the SOD1 is responsible for FALS with broader pathological involvement.
authors.affiliation: Department of Neurology, Niigata University, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Inuzuka
authors.forename: K
authors.initials: K
authors.lastname: Sakimura
authors.forename: M
authors.initials: M
authors.lastname: Mishina
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: F
authors.initials: F
authors.lastname: Ikuta
authors.forename: Y
authors.initials: Y
authors.lastname: Honma
authors.forename: J
authors.initials: J
authors.lastname: Fujii
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004795:Enzyme Stability / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009036:Moths; D010375:Pedigree; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase