title: SOD1 mutations in amyotrophic lateral sclerosis. Results from a multicenter Italian study.
abstract: Amyotrophic Lateral Sclerosis (ALS), the most common form among motoneuron diseases, is characterized by a progressive neurodegenerative process involving motor neurons in the motor cortex, brain stem and spinal cord. Sporadic (SALS) accounts for the majority of patients but in about 10% of ALS cases the disease is inherited (FALS), usually as an autosomal dominant trait. In the present study we show the results of a referred based multicenter study on the distribution of SOD1 gene mutations in the largest cohort of Italian ALS patients described so far. Two hundred and sixty-four patients (39 FALS and 225 SALS) of Italian origin were studied. In 7 out of 39 FALS patients we found the following SOD1 gene mutations: i) a new G12R missense mutation in exon 1, found in a patient with a slowly progressive disease course; ii) the G41S mutation, in four unrelated patients with rapidly progressive course complicated with cognitive decline in two of them; iii) the L114F mutation, in a patient with a slowly progressive phenotype; iv) the D90A mutation, in a heterozygous patient with atypical phenotype. In addition, in one SALS patient a previously reported synonymous variant S59S was identified. In 17 (3 FALS and 14 SALS) out of 264 patients (6.4 %) the polymorphism A-->C at position 34 of intron 3 (IVS3: + 34 A-->C) was found, and in one FALS patient a novel variant IVS3 + 62 T-->C was identified. The frequency of SOD1 gene mutations (17.9 %) in FALS cases was comparable with that found in other surveys with a similar sample size of ALS cases. No SOD1 gene mutations have been identified in SALS cases. Within FALS cases, The most frequent mutation was the G41S identified in four FALS.
authors.affiliation: Dept. of Neuroscience, University of Siena, Siena, Italy. battistini@unisi.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Battistini
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Greco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bibbò
authors.forename: Loreta
authors.initials: L
authors.lastname: Ferrera
authors.forename: Valeria
authors.initials: V
authors.lastname: Marini
authors.forename: Renzo
authors.initials: R
authors.lastname: Causarano
authors.forename: Michela
authors.initials: M
authors.lastname: Casula
authors.forename: Giuliana
authors.initials: G
authors.lastname: Lando
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Patrosso
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marocchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Corona
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mascia
authors.forename: Marcello
authors.initials: M
authors.lastname: Giagheddu
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
authors.forename: Sandro
authors.initials: S
authors.lastname: Orrù
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garrè
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D015152:Blotting, Northern / Q000379:methods; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005192:Family Health; D005260:Female; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D007438:Introns; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012694:Serine / Q000235:genetics; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D012333:RNA, Messenger; C000606290:SOD1 protein, human; D012694:Serine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005998:Glycine