Exome Sequencing as a Diagnostic Tool for Pediatric‐Onset Ataxia. Issue 1 (13th November 2013)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Human mutation. Volume 35:Issue 1(2014:Jan.)
• Page Start: 45
• Page End: 49
• Publication Date: 2013-11-13
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22451
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>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.</p> </abstract>