Exome Sequencing as a Diagnostic Tool for Pediatric‐Onset Ataxia Academic Article uri icon

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  • Ataxia demonstrates substantial phenotypic and genetic heterogeneity. We set out to determine the diagnostic yield of exome sequencing in pediatric patients with ataxia without a molecular diagnosis after standard-of-care assessment in Canada. FORGE (Finding Of Rare disease GEnes) Canada is a nation-wide project focused on identifying novel disease genes for rare pediatric diseases using whole-exome sequencing. We retrospectively selected all FORGE Canada projects that included cerebellar ataxia as a feature. We identified 28 such families and a molecular diagnosis was made in 13; a success rate of 46%. In 11 families, we identified mutations in genes associated with known neurological syndromes and in two we identified novel disease genes. Exome analysis of sib pairs and/or patients born to consanguineous parents was more likely to be successful (9/13) than simplex cases (4/15). Our data suggest that exome sequencing is an effective first line test for pediatric patients with ataxia where a specific single gene is not immediately suspected to be causative.


  • Sawyer, Sarah L
  • Schwartzentruber, Jeremy
  • Beaulieu, Chandree L
  • Dyment, David
  • Smith, Amanda
  • Chardon, Jodi Warman
  • Yoon, Grace
  • Rouleau, Guy A
  • Suchowersky, Oksana
  • Siu, Victoria
  • Murphy, Lisa
  • Hegele, Robert A
  • Marshall, Christian R
  • Bulman, Dennis E
  • Majewski, Jacek
  • Tarnopolsky, Mark
  • Boycott, Kym M

publication date

  • January 2014