title: Mutations in rare ataxia genes are uncommon causes of sporadic cerebellar ataxia.
abstract: BACKGROUND
  Sporadic-onset ataxia is common in a tertiary care setting but a significant percentage remains unidentified despite extensive evaluation. Rare genetic ataxias, reported only in specific populations or families, may contribute to a percentage of sporadic ataxia.
  
  
  METHODS
  Patients with adult-onset sporadic ataxia, who tested negative for common genetic ataxias (SCA1, SCA2, SCA3, SCA6, SCA7, and/or Friedreich ataxia), were evaluated using a stratified screening approach for variants in 7 rare ataxia genes.
  
  
  RESULTS
  We screened patients for published mutations in SYNE1 (n = 80) and TGM6 (n = 118), copy number variations in LMNB1 (n = 40) and SETX (n = 11), sequence variants in SACS (n = 39) and PDYN (n = 119), and the pentanucleotide insertion of spinocerebellar ataxia type 31 (n = 101). Overall, we identified 1 patient with a LMNB1 duplication, 1 patient with a PDYN variant, and 1 compound SACS heterozygote, including a novel variant.
  
  
  CONCLUSIONS
  The rare genetic ataxias examined here do not significantly contribute to sporadic cerebellar ataxia in our tertiary care population.
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA. bfogel@ucla.edu
authors.forename: Brent L
authors.initials: BL
authors.lastname: Fogel
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Jessica
authors.initials: J
authors.lastname: Lane
authors.forename: Amanda
authors.initials: A
authors.lastname: Wahnich
authors.forename: Sandy
authors.initials: S
authors.lastname: Chan
authors.forename: Alden
authors.initials: A
authors.lastname: Huang
authors.forename: Greg E
authors.initials: GE
authors.lastname: Osborn
authors.forename: Eric
authors.initials: E
authors.lastname: Klein
authors.forename: Catherine
authors.initials: C
authors.lastname: Mamah
authors.forename: Susan
authors.initials: S
authors.lastname: Perlman
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
mesh_terms: D000328:Adult; D000368:Aged; D002524:Cerebellar Ataxia / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004265:DNA Helicases; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D034921:Lamin Type B / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064251:Multifunctional Enzymes; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics*; D020365:RNA Helicases / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D004745:Enkephalins; D006360:Heat-Shock Proteins; D034921:Lamin Type B; D064251:Multifunctional Enzymes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; C404403:SACS protein, human; C415465:SYNE1 protein, human; C033660:preproenkephalin; C532876:TGM6 protein, human; D011503:Transglutaminases; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases