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Exome Sequencing as a Diagnostic Tool for Pediatric‐Onset Ataxia
Author(s) -
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 year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22451
Subject(s) - exome sequencing , ataxia , biology , exome , genetics , rare disease , disease , genetic testing , human genetics , bioinformatics , gene , phenotype , medicine , pathology , neuroscience
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 C anada. FORGE (Finding Of Rare disease GEnes) C anada is a nation‐wide project focused on identifying novel disease genes for rare pediatric diseases using whole‐exome sequencing. We retrospectively selected all FORGE C anada 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.