title: A novel codon4 mutation (A4F) in the SOD1gene in familial amyotrophic lateral sclerosis.
abstract: We identified a novel missense mutation in the Cu/Zn superoxide dismutase (SOD1) gene in a 47-year-old woman with familial amyotrophic lateral sclerosis (ALS). The heterozygous mutation, in exon 1 of the SOD1 gene, is a GC to TT transversion in nucleotide positions 13 and 14 leading to an alanine 4 to phenylalanine (A4F) amino acid substitution. It was found in six family members. The effect of the A4F mutation was of similar severity to that of the A4V mutation. We discuss structural instability as a possible pathogenic mechanism in the case of this SOD1 mutation. The proband displayed upper motor neuron signs not observed in individuals with other codon 4 mutations. This could be because longer survival allows UMN dysfunction to become evident. We also provide a literature review.
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Wonki
authors.initials: W
authors.lastname: Baek
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Park
authors.forename: Young Seo
authors.initials: YS
authors.lastname: Kim
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000409:Alanine / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D010649:Phenylalanine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000409:Alanine