SOD1 mutations in amyotrophic lateral sclerosis

• DOI: 10.1007/s00415-005-0742-y
• Publication Date: 2005-03-23T15:37:00Z
• Authors: S. Battistini; F. Giannini; G. Greco; G. Bibbò; L. Ferrera; V. Marini; R. Causarano; M. Casula; G. Lando; M. C. Patrosso; C. Caponnetto; P. Origone; A. Marocchi; A. Del Corona; G. Siciliano; P. Carrera; V. Mascia; M. Giagheddu; C. Carcassi; S. Orrù; C. Garrè; S. Penco
• Keywords: Amyotrophic lateral sclerosis; Clinical features; Motor neuron disease; Multicenter study; SOD1 gene; Adult; Male; Adolescent; Genotype; DNA Mutational Analysis; Glycine; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Humans; Motor neuron disease; Amyotrophic lateral sclerosi; Aged; Aged, 80 and over; Family Health; Amyotrophic Lateral Sclerosis; Exons; Middle Aged; Blotting, Northern; Multicenter study; Introns; Pedigree; Clinical feature; Italy; Mutation; Female; SOD1 gene

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.