Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene

Stefania Battistini, Claudia Ricci, Enrico Maria Lotti, Michele Benigni, Stella Gagliardi, Riccardo Zucco, Massimo Bondavalli, Norina Marcello, Mauro Ceroni, Cristina Cereda

Research output: Contribution to journalArticle

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with a positive familial history in 5-10% of ALS cases. Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS. Here we report a novel mutation in exon 4 of SOD1 gene in a 55-year-old ALS patient belonging to a large Italian family with ALS first clinically described in 1968. In the family the clinical presentation was characterized by relatively early age of onset, spinal onset with proximal distribution weakness, bulbar involvement and a rapid disease course. Molecular analysis showed a heterozygous mutation at codon 106 resulting in a substitution of phenylalanine for leucine in the SOD1 protein (L106F). In analogy with the previously reported L106V mutation, we propose that the L106F causes a relevant destabilization of the protein chain around the mutation site, able to affect the SOD1 monomer and dimer structures suggesting a pathogenic role for this novel mutation.

Original languageEnglish
Pages (from-to)112-115
Number of pages4
JournalJournal of the Neurological Sciences
Volume293
Issue number1-2
DOIs
Publication statusPublished - Jun 15 2010

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Keywords

  • Amyotrophic Lateral Sclerosis
  • Familial ALS
  • Mutation
  • Protein structural modelling
  • Superoxide dismutase 1 (SOD1) gene

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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