title: Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism?
abstract: BACKGROUND
  Hereditary spastic paraplegias (SPG1-SPG33) are characterized by progressive spastic weakness of the lower limbs. A nucleotide deletion (1110delA) in the (SPG20; OMIM 275900) spartin gene is the origin of autosomal recessive Troyer syndrome. This mutation is predicted to cause premature termination of the spartin protein. However, it remains unknown whether this truncated spartin protein is absent or is present and partially functional in patients.
  
  
  OBJECTIVE
  To determine whether the truncated spartin protein is present or absent in cells derived from patients with Troyer syndrome.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  We describe a new family with Troyer syndrome due to the 1110delA mutation.
  
  
  METHODS
  We cultured primary fibroblasts and generated lymphoblasts from affected individuals, carriers, and control subjects and subjected these cells to immunoblot analyses.
  
  
  RESULTS
  Spartin protein is undetectable in several cell lines derived from patients with Troyer syndrome.
  
  
  CONCLUSIONS
  Our data suggest that Troyer syndrome results from complete loss of spartin protein rather than from the predicted partly functional fragment. This may reflect increased protein degradation or impaired translation.
authors.affiliation: Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3704, USA.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Bakowska
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Baozhong
authors.initials: B
authors.lastname: Xin
authors.forename: Charlotte J
authors.initials: CJ
authors.lastname: Sumner
authors.forename: Craig
authors.initials: C
authors.lastname: Blackstone
mesh_terms: D001483:Base Sequence / Q000235:genetics; D018797:Cell Cycle Proteins; D003241:Consanguinity; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018703:Founder Effect; D016368:Frameshift Mutation; D015870:Gene Expression / Q000235:genetics; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D009711:Nucleotides / Q000235:genetics; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: D018797:Cell Cycle Proteins; D009711:Nucleotides; D011506:Proteins; C464787:SPART protein, human