title: Variable clinical symptoms in familial amyotrophic lateral sclerosis with a novel point mutation in the Cu/Zn superoxide dismutase gene.
abstract: We report a novel missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene of affected members of a Japanese kindred segregating familial amyotrophic lateral sclerosis (FALS) through at least three successive generations. The mutation, which is predicted to cause the replacement of isoleucine at codon 104 by phenylalanine (I104F), is associated with a significant reduction in Cu/Zn SOD enzyme activity but results in a highly variable clinical phenotype. Age at onset varied from 6 to 55; the initial symptoms occurred in either the lower or upper extremities in different family members. The duration of the disease varied from 3 to 38 years. Two subjects, aged 59 and 34, remained asymptomatic until their death from other causes, although their offspring carrying the same mutation have already developed clinical evidence of the disease. These results suggest that FALS from this novel I104F mutation shows considerable clinical variation.
authors.affiliation: Department of Neurology, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Sahara
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
authors.forename: S
authors.initials: S
authors.lastname: Hirai
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D003300:Copper; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D015032:Zinc
chemical_list: D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc