title: An analysis of the entire SOD1 gene in sporadic ALS.
abstract: Mutations in the superoxide dismutase 1 gene (SOD1) are associated with familial ALS but the role of SOD1 in sporadic ALS (SALS) is unclear. We therefore sequenced the entire SOD1 gene in 23 patients with SALS. DNA was extracted from frozen pre-frontal cerebral cortex and from blood. The 5 exons, 4 introns and 1 kb upstream and downstream of SOD1 were sequenced. Novel genetic variants were found in 30% (7 of 23) brains and known variants in 91% (21 of 23) brains from patients with SALS. Two novel variants found in SALS patients and not controls were located in the SOD1 promoter and intron 1, with the promoter variant having potential functional implications. A previously described silent variant in exon 5 in one SALS patient appears to abolish an exonic splicing enhancer. All changes found in brain DNA were also found in blood DNA. In conclusion, sequencing the entire SOD1 gene revealed 3 variants in SALS patients that were not detected in controls. Although no unequivocal mutations were found, some of these variants have potential consequences for SALS pathogenesis.
authors.affiliation: Department of Pathology, Blackburn Building D06, The University of Sydney, NSW 2006, Australia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Luquin
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Trent
authors.forename: Julia M
authors.initials: JM
authors.lastname: Morahan
authors.forename: Roger
authors.initials: R
authors.lastname: Pamphlett
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D013482:Superoxide Dismutase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1