title: The IVS1 +319 t>a of SOD1 gene is not an ALS causing mutation.
abstract: Amyotrophic lateral sclerosis (ALS) is caused by mutations in the gene for Cu/Zn superoxide dismutase (SOD1) in 10% of familial and sporadic cases. During the SOD1 analysis of 9 FALS and 121 SALS, in only one sporadic case we found the exonic mutation N19S; in 15 SALS patients we found a 319t>a variation in IVS1 sequence, at 108 bp upstream from exon 2. This variation has an unusually high frequency of 11% and is always in linkage disequilibrium with a described polymorphism in IVS3, +34a>c. The 319t>a variation is classified in two different public databases, HGMD and The ALS Online Database, as a splicing mutation and not as a polymorphism. The unusually high frequency of this mutation in our patients prompted us to determinate its frequency in 130 age- and gender- matched healthy controls and in 54 patients with Alzheimer's disease. We found again linkage disequilibrium with the polymorphism in intron 3, and the frequency of 11% and 7.8%, respectively. These results strongly support the idea that the IVS1 +319 t>a alone is not an ALS causing mutation, and that special care must be taken in the interpretation of data from mutations databases for correct genetic counselling.
authors.affiliation: S.C.Molecolare, Dipartmento di Patalogia Clinica, A.O.O.I.R.M.-S. Anna, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Restagno
authors.forename: A
authors.initials: A
authors.lastname: Gomez
authors.forename: F
authors.initials: F
authors.lastname: Lombardo
authors.forename: E
authors.initials: E
authors.lastname: Cocco
authors.forename: A
authors.initials: A
authors.lastname: Calvo
authors.forename: P
authors.initials: P
authors.lastname: Ghiglione
authors.forename: R
authors.initials: R
authors.lastname: Mutani
authors.forename: A
authors.initials: A
authors.lastname: Chiò
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1