Received: 5 February 2017
Revised: 6 March 2017
Accepted: 14 March 2017
DOI: 10.1111/cge.13024
ORIGINAL ARTICLE
Clinical genetic testing in pediatric cardiomyopathy: Is bigger better? A.C. Ouellette1
| J. Mathew2 | A.K. Manickaraj1 | G. Manase1 | L. Zahavich1 | J. Wilson1 |
K. George1 | L. Benson1 | S. Bowdin1 | S. Mital1 1 Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Background: For clinical genetic testing of cardiomyopathy (CMP), current guidelines do not address which gene panels to use: targeted panels specific to a CMP phenotype or expanded (panCMP) panels that include genes associated with multiple phenotypic subtypes.
2
Cardiology Department, The Royal Children’s Hospital, Melbourne, Victoria, Australia
Aim: Our objective was to assess the clinical utility of targeted versus panCMP panel testing in
Correspondence Seema Mital, MD, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Email:
[email protected]
(n = 8), or left-ventricular non-compaction (n = 13) CMP who underwent clinical genetic panel
Funding information Ted Rogers Centre for Heart Research; Heart and Stroke Foundation of Ontario Chair in Cardiovascular Science; University of Toronto Institute of Medical Sciences Summer Undergraduate Research Program.
pediatric CMPs. Methods: 151 pediatric patients with primary hypertrophic (n = 66), dilated (n = 64), restrictive testing at a single centre were included. PanCMP (n = 47) and targeted panel testing (n = 104) were compared for yield of pathogenic variants and variants of unknown significance (VUS). Results: Pathogenic variants were identified in 26% of patients, 42% had indeterminate results (only VUS detected), and 32% had negative results. Yield was lower (15%) in panCMP vs. targeted panel testing (32%) (P = .03) in all CMP subtypes. VUS detection was higher with panCMP (87%) than targeted panel testing (30%) (P
