title: Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis.
abstract: OBJECTIVE
  Recessive mutations in ALS2 (juvenile amyotrophic lateral sclerosis) are causative for early-onset upper motor neuron diseases, including infantile ascending hereditary spastic paralysis (IAHSP). The goal of this study is to identify novel disease-causing ALS2 mutations.
  
  
  METHODS
  Mutations in ALS2 were screened by direct sequencing of complementary DNA obtained from patients' lymphoblasts.
  
  
  RESULTS
  We report a novel ALS2 missense mutation in patients affected by IAHSP. This homozygous G669A mutation in exon 4 is predicted to result in a tyrosine substitution at cysteine 156 of the RCC1 (regulator of chromatin condensation)-like domain, encoding a putative guanine exchange factor for Ran guanosine triphosphatase, leading to a loss of ALS2 function due to instability of mutant protein.
  
  
  CONCLUSIONS
  These results highlight the important role of the RCC1-like domain in ALS2 stability and function that is essential for upper motor neuron maintenance.
authors.affiliation: Institut National de la Sante et de la Recherche Médicale U384 and Human Genetics Department, CHU, Clermont-Ferrand, France.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Martin
authors.initials: M
authors.lastname: Haeussler
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.forename: Fernande
authors.initials: F
authors.lastname: Gauthier-Barichard
authors.forename: Patricia
authors.initials: P
authors.lastname: Combes
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D012689:Sequence Homology, Nucleic Acid; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: C438187:ALS2 protein, human; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C062521:RCC1 protein, human