ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 252, Issue 7, pp 782-788

SOD1 mutations in amyotrophic lateral sclerosis

Results from a multicenter Italian study
  • S. BattistiniAffiliated withDept. of Neuroscience, University of SienaDept. of Neuroscience—Neurology Section, University of Siena Email author 
  • , F. GianniniAffiliated withDept. of Neuroscience, University of Siena
  • , G. GrecoAffiliated withDept. of Neuroscience, University of Siena
  • , G. BibbòAffiliated withDept. of Neuroscience, University of Siena
  • , L. FerreraAffiliated withDept. of Oncology Biology and Genetics, University of Genova
  • , V. MariniAffiliated withDept. of Oncology Biology and Genetics, University of Genova
  • , R. CausaranoAffiliated withDept. of Neuroscience, Niguarda Ca’ Granda Hospital
  • , M. CasulaAffiliated withDept. of Medical Sciences, Medical Genetics University of Cagliari
  • , G. LandoAffiliated withClinical Chemistry and Clinical Pathology Laboratory, Niguarda Ca’ Granda Hospital
    • , M. C. PatrossoAffiliated withClinical Chemistry and Clinical Pathology Laboratory, Niguarda Ca’ Granda Hospital
    • , C. CaponnettoAffiliated withDept. of Neurosciences, Ophthalmology and Genetics, University of Genova
    • , P. OrigoneAffiliated withDept. of Oncology Biology and Genetics, University of Genova
    • , A. MarocchiAffiliated withClinical Chemistry and Clinical Pathology Laboratory, Niguarda Ca’ Granda Hospital
    • , A. Del CoronaAffiliated withDept. of Neuroscience, University of Pisa
    • , G. SicilianoAffiliated withDept. of Neuroscience, University of Pisa
    • , P. CarreraAffiliated withIRCCS H San Raffaele, Clinical Molecular Biology Laboratory
    • , V. MasciaAffiliated withDept. of Neuroscience, University of SienaInstitute of Neurology, University of Cagliari
    • , M. GiaghedduAffiliated withDept. of Neuroscience, University of SienaInstitute of Neurology, University of Cagliari
    • , C. CarcassiAffiliated withDept. of Medical Sciences, Medical Genetics University of Cagliari
    • , S. OrrùAffiliated withDept. of Medical Sciences, Medical Genetics University of Cagliari
    • , C. GarrèAffiliated withDept. of Oncology Biology and Genetics, University of Genova
    • , S. PencoAffiliated withClinical Chemistry and Clinical Pathology Laboratory, Niguarda Ca’ Granda Hospital

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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.

Key words

amyotrophic lateral sclerosis SOD1 gene multicenter study clinical features motor neuron disease