SickKids.ca landing page TCAG main landing page DGV site PGP site CGEn site News on University of Waterloo award

News 2015

Whole Exome Sequencing and Targeted Copy Number Analysis in Primary Ciliary Dyskinesia

Christian R. Marshall1, Stephen W. Scherer2, Maimoona A. Zariwala3, Lynette Lau1, Tara A. Paton1, Tracy Stockley1, Rebekah K. Jobling1, Peter N. Ray1, Michael R. Knowles3, David A. Hall4, Sharon D. Dell2 and Raymond H. Kim

Abstract

Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder resulting from loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus and infertility. Clinical features may be subtle and highly variable making the diagnosis of PCD challenging. The diagnosis can be confirmed with ciliary ultrastructure analysis and/or molecular genetic testing of 32 PCD associated genes. However, due to this genetic heterogeneity, comprehensive molecular genetic testing is not considered standard of care, and the most efficient molecular approach has yet to be elucidated. Here, we propose a cost-effective and time-efficient molecular genetic algorithm in solving PCD cases. We conducted targeted copy number variation (CNV) analysis and/or whole exome sequencing (WES) on 20 families (22 patients) from a subset of 45 families (52 patients) with a clinical diagnosis of PCD who did not have a molecular genetic diagnosis after Sanger sequencing of 12 PCD associated genes. This combined molecular genetic approach led to the identification of 4/20 (20%) families with clinically significant CNVs and 7/20 (35%) families with biallelic pathogenic mutations in recently identified PCD genes, resulting in an increased molecular genetic diagnostic rate of 55% (11/20). In patients with a clinical diagnosis of PCD, WES before targeted CNV analysis results in an overall molecular genetic yield of 76% (34/45).

Address correspondence to: raymond.kim@utoronto.ca

Download full text article

Copyright © 2015 Author et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


For questions or comments contact the TCAG Manager,

Copyright 1999-2019 The Hospital for Sick Children (SickKids). All rights reserved. The Hospital for Sick Children (SickKids) is a health-care,
teaching and research centre dedicated exclusively to children; affiliated with the University of Toronto. For general inquires please call: 416-813-1500.
Terms and Conditions | Acknowledgment Policy
Contact SickKids | Terms of Use | Sitemap