title: The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings.
abstract: Eight mutations in the ALS2 gene have been described as causing autosomal-recessive juvenile-onset forms of the motor neuron diseases amyotrophic lateral sclerosis, primary lateral sclerosis and hereditary spastic paraplegia. All mutations are small deletions that are predicted to result in a frameshift and premature truncation of the alsin protein. Here we describe a ninth ALS2 mutation, in two siblings affected by infantile-onset ascending spastic paraplegia with bulbar involvement. This mutation is predicted to result in the substitution of an amino acid by a stop codon, and thus is the first nonsense mutation detected in this gene. It is probable that full-length alsin is required for the proper development and/or functioning of upper motor neurons.
authors.affiliation: Department of Medical Genetics, University of British Columbia, and Children and Women's Hospital, Vancouver, British Columbia, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Devon
authors.forename: J R
authors.initials: JR
authors.lastname: Helm
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Y
authors.initials: Y
authors.lastname: Leitner
authors.forename: T
authors.initials: T
authors.lastname: Lerman-Sagie
authors.forename: D
authors.initials: D
authors.lastname: Lev
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D017668:Age of Onset; D018389:Codon, Nonsense; D003241:Consanguinity; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007585:Jews / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D020828:Pseudobulbar Palsy / Q000235:genetics* / Q000473:pathology; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; D020033:Protein Isoforms