Mutations of the ANG gene in French patients with sporadic amyotrophic lateral sclerosis

Arch Neurol. 2008 Oct;65(10):1333-6. doi: 10.1001/archneur.65.10.1333.

Abstract

Background: Mutations in the angiogenin gene, ANG, have been associated recently with familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown.

Objective: To assess the frequency of ANG gene mutations in 855 French patients with sporadic ALS.

Design: We analyzed by direct sequencing the full coding region of the ANG gene in a cohort of French patients with sporadic ALS. The clinical characteristics of patients carrying ANG mutations are detailed.

Setting: French ALS Study Group. Patients A total of 855 patients with sporadic ALS.

Main outcome measures: Results of genetic analyses.

Results: We observed a previously identified mutation (pI46V) in 2 patients with ALS without a known family link and found a novel mutation (pR121H) in 1 patient who developed ALS with rapid progression. We did not observe an association between patients with ALS and the rs11701 polymorphism, as previously reported in certain ALS populations of other ethnic origins.

Conclusion: Overall, our findings support the implication of ANG gene mutations as a rare but widespread cause of ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / blood
  • Amyotrophic Lateral Sclerosis / epidemiology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Catalytic Domain / genetics
  • Central Nervous System / metabolism
  • Central Nervous System / physiopathology
  • Cohort Studies
  • DNA Mutational Analysis / methods*
  • Female
  • France / epidemiology
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protein Structure, Tertiary / genetics
  • Ribonuclease, Pancreatic / blood
  • Ribonuclease, Pancreatic / genetics*

Substances

  • Genetic Markers
  • angiogenin
  • Ribonuclease, Pancreatic