Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis

Cinzia Gellera, Claudia Colombrita, Nicola Ticozzi, Barbara Castellotti, Cinzia Bragato, Antonia Ratti, Franco Taroni, Vincenzo Silani

Research output: Contribution to journalArticle

Abstract

Angiogenin (ANG) gene, coding for an angiogenic factor up-regulated by hypoxia and expressed in ventral horn motor neurons, is a novel candidate for the pathogenesis of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the selective loss of cortical and spinal motor neurons. Missense mutations in ANG gene have been identified in two ALS populations from Northern Europe and North America, both in familial (FALS) and sporadic (SALS) patients, but they do not seem to be frequent in the Italian population. We performed a mutational screening in a large cohort of 737 Italian ALS patients, including 605 SALS and 132 FALS cases. We identified seven different mutations, five of which are novel, in nine patients (six SALS and three FALS), but not in 515 healthy controls. Three mutations are located in the signal peptide region, three in the coding sequence, and one in the 3′ untranslated region. In our ALS population, the observed mutational frequency of ANG gene accounts for about 1.2%, with an overrepresentation of FALS (2.3%) compared to SALS (1%) cases. We also found the previously described I46V substitution in six patients and four controls, suggesting that this mutation may represent a benign variant, at least in the Italian population. Our results provide further evidence of a tight link between angiogenesis and ALS pathogenesis and suggest that mutations in ANG gene are associated with an increased risk to develop ALS.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalNeurogenetics
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Amyotrophic lateral sclerosis
  • Angiogenin
  • Case-control studies
  • Motor neuron disease
  • Risk factors

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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