title: G41S SOD1 mutation: A common ancestor for six ALS Italian families with an aggressive phenotype.
abstract: More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 (SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype.
authors.affiliation: Department of Neuroscience, University of Siena, Italy. battistinis@unisi.it <battistinis@unisi.it>
authors.forename: Stefania
authors.initials: S
authors.lastname: Battistini
authors.forename: Claudia
authors.initials: C
authors.lastname: Ricci
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.forename: Silvia
authors.initials: S
authors.lastname: Calzavara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Greco
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Corona
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Noè
authors.initials: N
authors.lastname: Battistini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology*; D018450:Disease Progression; D005192:Family Health; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1